I just for putting together this amazing meeting and for inviting me, I'm really happy to be here and really excited to meet and discuss with people at the meeting. So to sort of position the interests of my lab as an introduction, us like most everybody in the room is interested in figuring out how the brain works, how it generates sensory perception, motor control, cognition, and then perhaps try and understand how those psychiatric and neurodegenerative disease make cripple in a brain function. Now we tackle these questions at the level of nervous circuits because nervous circuits are sort of the basic computational units the brain uses. So for example here, motor neurons in the spinal cord are essentially components of the sensory motor circuit that controls the movement of our limbs. Now I'm particularly fascinated in the diversity of the different types of neurons that constitute such neural circuits. This is evident at the cellular molecular levels. So for here, for example, again, motor neurons, but now distinct types of motor neurons labeled by distinct types or distinct patterns of gene expression. This diversity of cell types is very obvious at the morphological level. It's obvious at the, or it's very prominent at the level of local long range connectivity and perhaps most importantly at the level of functional and intrinsic properties. And I would argue that understanding neural diversity is one of the key challenges in trying to understand neural circuit function. So we chose the olfactory cortex. Pyrofoam cortex is our model system for the following reasons. So first, as you've heard throughout the meeting, olfaction is of outstanding ethological importance. Animals mice really care about what they smell. And this tight link allows us to establish causal relationships between circuit function and behavior. Olfactory cortex is a sophisticated thing. So it integrates segregated input channels from the olfactory bulb to create all the objects or all the perception. It also links all the perception to experience and learning and memory. So it has essential functions in associative olfactory learning and memory. Now, both in humans and in mouse models, the olfactory system is tightly linked to social and emotional behaviors aging and all degenerative disease. So there's a considerable interest in understanding olfactory circuit function from a translational perspective. However, for us, the most important reason we study olfactory cortex because it's a comparatively simple cortical circuit. And I'll go into that in a minute. As has been pointed out throughout the meeting, the odorants are detected in the olfactory betelion by odorant receptors expressed on olfactory sensory nons. These nons project to the olfactory bulb and nons expressing the same receptor can coalesce into individual glomerular olfactory bulbs such that others elicit these discrete segregated patterns of glomerular activity. Now, what I would like to point out the stress is that in order for us to perceive odors to generate these odor objects we can describe and that animals can report to us in terms of behavior, this segregated information has to be integrated. And this integration happens in olfactory cortex. So how is information transmitted from the bulb to the cortex? Michael and Tufted says, as Florin explained very nicely in the previous talk, project to large areas in the brain. This is the waveform cortex here. And in contrast to this segregated tight organization of projections to the olfactory bulb, these projections are widespread and diffuse and as such allow for the integration of different glomerular input channels. And consistent with this anatomy, both imaging data and electrophysiology have shown quite clearly that odors activate these very distributed patterns of nodal activity in waveform cortex. Now, olfactory cortex is close to the periphery as also Charlie introduced is only two synapses away from the sensory neuron and it's also relatively simple in organization. So olfactory cortex sits here at the bottom of the brain. This is the coronal section for the mouse brain below and the neocortex here is composed of three layers, layer one containing the main input axons from micron tufted cells synapses onto dendrites of principal cells in layers two and three which then form a large recurrent network and also accommodate associative top-down inputs from other cortical and sub-cortical areas. However, how these circuit functions emerge from the concerted activity of different types of nods in waveform cortex is fully understood and that's what I will try to address a little bit in during my talk. So I'll be discussing two sets of experiments. First, a set of positive imaging experiments which allow us to better understand how information about odors is encoded in olfactory neural circuits in the cortex. These data also highlights the functional diversity of different neurons in cortex. A second set of experiments where we use molecular genetics to identify markers and molecular signatures that identify the linear different types of nods and their connectivity patterns. And then I'll spend a little bit of time to illustrate where we're taking these experiments next. So to explore, and this is following up nicely on Florence talk with a lot of sort of overlapping interests and techniques. So to explore sensory processing in olfactory cortex, we use two photon imaging. So we stair-toxically inject the calcium indicator six, a G-Camp six into BFM cortex. The experiments I'll describe are performed in anesthetized animals which is a big caveat on one hand. On the other hand, we have now both with Kevin Franks, electrophysiology in awake and anesthetized animals and preliminary new data, imaging data in awake animals which really demonstrate that the kinds of parameters we use for the analysis I'll describe are fairly conserved across brain states and we're fairly confident that they're generally relevant. But I'll be happy to discuss that later. So this is what it looks like when we infect period from neurons. These are all the responses which you may have seen. So color coded from blue to red. These are very densely labeled areas. So we have to develop an algorithm to actually segment these cells in an automated fashion. So this algorithm uses correlation over time like many other algorithms but also takes into account spatial constraints and much works very well in particular for such densely labeled areas in the brain. And these are just the next slide are just some example responses of such experiments. So these are 12 different norms I believe in lines and 13 different order stimuli and there's basically two things we observe. First of all, the response properties we observe are very diverse. So we see neurons that respond with an increase in activity indicated in red, with a decrease in activity indicated in blue. There's neurons that are very broadly tuned that will respond to pretty much every order you give them. There's neurons that are very selective for particular odorants. There's neurons that are very reproducibly responded across different trials. Others that show a lot of trial to trial variability, et cetera. And so we can map these responses now back onto the imaging site and that's shown here. And we see these dispersed order responses that are consistent with previously published data. Now what's different here with this increased resolution both temporal and spatial or higher signal or noise is that we can use single trial instead of averaging. And that sort of highlights two important features of these responses. One is that there's a lot of trial to trial variability. So you see, for example, these neurons here responding to acetate and trial number one, they respond again, one disappears, the other one is active, the other one comes back, one disappears, et cetera. So across trials, about 50, 60% of neurons kind of come and go and there's a lot of variability that works. It's coming out of this, but it's very serious. Right, so we did this experiment, it's very low. We see about 10 to 15% active neurons spontaneous activities in the range of one to three percent. So over the same, yeah, if we do the same types of windows. The other aspect is that a lot of neurons show very overlapping response properties. So you see that these two neurons here respond happily to all three neurons without much of a preference. And if you go through these patterns, you find a lot of them. So what that tells you is that looking at individual neurons really doesn't tell you anything about stimulus information. And so we have to reformat these data in such ways that we can quantitatively get at understanding what they may represent. So this is such a matrix or vector where the cells of the particular imaging site, about 280, 300 cells are lined up on the y-axis. There's 13 different orders and four files each so that each data point represents the response average change in fluorescence over a short period of time after stimulus onset. And with these matrices, we can now begin to quantitatively compare and calculate similarities and differences in the response patterns to different orders. So in such a simple way by calculating the correlations. And what you see here is that so correlation, I mean similarities between one and the same stimulus per definition one is on the diagonal here. And this makes two points really that so four trials of hexanol, for example, are fairly correlated to each other and different from other order and that's true for some. But if you, for example, look up here at citronol, then you see that there's a lot of heterogeneity or sort of dissimilarity between different citronol trials and the similarities fairly equal across the different sets of orders, which reflects the sort of overlapping and trial to trial variability. Yes. So the orders are pseudo randomized such that we never use the same order twice in a row and the intertrial intervals are two minutes. We've done this with longer intertrial intervals, et cetera. And I think we're fairly confident that none of that reflects a bit duration, I think like four in this case, four to seven. So about 50 to 60% of neurons will respond on consecutive trials and the other half of neurons kind of come in and out. And so, no, come yet, why is it about the same? Half of the neurons will respond. Will respond all four times. No, will respond in consecutive trials and then they come back at some point later and we haven't done that in extensively enough. A man as such that we can ask how, what's the percentage of neurons total that would respond to a particular order and I cannot tell you that? Oh, yes. Absolutely. Right, right. Yes, I'll have to think if there's some logic to that. I can remember that. All cells have a different image in this case. Okay, so to more directly ask if these patterns are different such that they can be discriminated, we use the classifiers similar to what had been discussed before and this is now based on again a single imaging site and works pretty well so using a linear classifier we can predict based on single trial response patterns with an accuracy of above 70% the identity of an order within this order set of certain different orderants and if we combine our windows either within the mouse or across mice then we can very quickly reach accuracies that go beyond 80, 90% which is consistent with the physiology data. So which layer and waveform cortex? So we've played a lot with layers. I'll come back to that later. From my perspective, it's not always flat and so guessing as to where you are within a layer is not a good reference but I'll come back to that in a minute. So basically this tells us that in the response patterns we image contain sufficient information to predict the identity of an order. We can then ask how is this information distributed across peer-reformed cortex? Is it organized? Is it clustered? Or is it distributed as previously suggested? So these are 250. This is one imaging site on average 220, remember? If you generate pseudo populations by adding imaging sites then that's what you get. So we need about 200, 150 to 300 neurons to come to an accuracy of above 70%. The green is fluorescence in fact because so we're using very slow ways of dealing with that and there's a delay in classification which is entirely explained by the delay in fluorescence. 13, it's the same order set that is that order set. It's 13 orders and so the tens level is here, 7%. So very little time to be the trial correlation itself, right? So what, right, if you look at the, yeah, we'll get something to tie in. So the number is 0.6 on average, yeah. 0.6 correlation on average with it, 0.6. Right. And across this order set, the number is 0.45. The linear claspy results are a different order set. No, no, that's the same order set using a linear clasifier but just looking at correlations that I don't think we've, these are Pearson correlation but we've done, basically they tell you that there's some consistency and some noise we didn't really look into that. So maybe last quick question. Yes, yes, yes. And again, we've done several ways of classifying and it basically comes out in very similar way. This is Euclidean. Yes. So I'll come, maybe I'll come back to that in a minute. Yes, in fact we've done it with microcells and I'll show you the results. Okay, so we're looking at how this information is organized in space and we did the following experiments. So if information is closed, okay. So we calculated the amount of information contained in ensembles of increasing size and we built these ensembles from starter cells and then either built them with cells that around the starter cells, especially constrained clusters of increasing size around the starter cell or increasing size ensembles that are randomly put together. And the prediction is that if information is clustered in some way, then ensembles built from specially constrained starter cells should differ in their information content and should be different from randomly assembled clusters of known weight. And so without going into detail the data suggests that there's no spatial organization, no clustering such that whether or not you built your ensembles from specially constrained or random populations we don't find any statistical measure that can differentiate between the efficiency or the accuracy of classifications built from these different types of ensembles, right? So now we use orders, we use order paths that are very controlled, very reproducible concentrations in the environment, in the wild, and as Andreas and others have pointed out, orders come in order plumes and one aspect of these order plumes is that the concentration of a given order and at a certain point in time massively varies, right? And as Linda has pointed out last time interactions of order and receptors and order and very strongly depend on the concentration of order and as such information on all activity that goes into the system will vary wildly depending on these fluctuations and concentrations within order plumes. Now on the other hand, perception of the identity of an order, identity, perception of an order must remain stable in these order plumes otherwise we'd constantly get confused as to what we're smelling and so the prediction has been that or one of the models has been that order representations in clear form cortex are concentration invariant that they allow us to decode the identity of an order independent of concentration, right? So we tested that by and this is just showing in fact that we can measure that with PID so these are order paths which most people use. If we take the PID a meter away and we open the window then we get these massive fluctuations that Andreas described in much more detail. So we tested how order representations in clear form in particular how order coding, identity coding in clear form depends on fluctuations in order concentration by using three orders at 10 fold and a hundred fold changing concentrations so 10,000, 1,000 and one in a hundred and basically going through the same sets of experiments and what you see is that overall the patterns of order evoked activity don't massively change with increasing concentration so we get few more norms that are active, we also get more norms that are suppressed. If we look at tuning at the specificity with which orders respond we can use lifetime sparseness here as a measure for that and we see that while individual norms change the tuning overall the distribution of tuning does it remain stable across this 100 fold range and concentration. It's liquid dilution but it's verified with PID measurement so it looks very reliable. Now if we start looking at individual norms however they do care about concentration and they do care quite a bit. So if you look for it so this is again one imaging side this is now clustered just to make it more visible. If we look at this cluster of norms here you see quite clearly that they are much more active in response to high concentrations of a set of inon whereas this cluster on top here basically shuts down at high concentrations of hexanone. So individual norms care about concentration so how does that affect the encoding of odd identity in pair from cortex? If we go back to simply calculating correlations then you see the following two things. So one is if we look at an individual order at last state at increasing concentrations the representations become more reliable and more similar and that likely simply reflects the fact that there's more signal over noise so we're using high concentrations, less noisy. More interesting however, if you look across concentrations now for it lasted you see that the response patterns gradually de-correlate so they turn from orange to blue and they're about as blue as all the other organs I showed you before which would suggest that as concentrations increase the patterns become very much indiscriminable amongst each other and very much sort of similar or as dissimilar as we observe for different order and that obviously poses a problem to the olfactory system and its need to stably encode odd identity. Second? So this looks exactly the same in the wake brain. So Kevin has done that in extra cell recordings we've done a little bit but this looks very much the same. There are differences which I'll be happy to discuss. So in order to solve a sort of get at this problem we wanted to test the idea that order identity is not encoded in the entire ensemble but that the order identity independent on concentration may be in fact encoded in a subnetwork or subpopulations of norms. And so the question then becomes can we isolate concentration and variance subpopulation of pure form norms and can these subpopulations provide any advantage for the system to generalize, to identify an order across different concentrations. And so we did that using linear regression where we first select norms that are significant and modulated by the identity and intensity of an order but we eliminate norms with mixed selectivity where there's an interaction between identity and intensity for simplicity at this point. And then we take norms that are significantly modulated by the order. So they care about which order they smell and we ask whether within that population there's a subpopulation of norms which doesn't care at which concentration they smell this order. So the question is do these norms exist? They're about 12% of all order responsive norms, about 30% of those that do care about the identity of an order and some example traces are shown here. And to verify this type of selection we compute the correlations. And what you see I think quite clearly is that now with this using the subnetwork or subpopulation of norms we generate fairly homogeneous correlations across now a hundred fold range of concentration, okay? And so we can now go ahead and compare the coding properties of this subnetwork with the entire rest of the norms by for example projecting these patterns in PCA space and looking at its structure. And what you see is that while generic norms so all the other norms cluster primarily by concentration so all the low concentration orders are here independent of identity, concentration in their networks now cluster by the identity of an order but within that cluster they don't care about concentration and we can ask more directly does this subnetwork enhance the capability of the system to generalize that is to predict the identity of an order independent of its concentration. For that we went back to linear classifier and now these are a little bit difficult to read but what we did is we trained the classifier on a set of orders and concentrations and then tested it with an order at the concentration that it was not trained with. So that's asking to identify an order at the concentration that it's never encountered before which we think more accurately so reflects the challenges of the olfactory system in real life. And what you see is that for 10 fold range in concentration so these are here anywhere in yellow for example for this order the both generic norms and the concentration and band subnetwork does reasonably okay with an accuracy of about 70% but if you go to a more drastic change in concentration as a hundred fold then you see that the subnetwork very significantly outperforms all the other norms in predicting the identity of the order. So yeah so this is in fact a fairly complicated question because it's very much dependent on our data set. So we've done that by so that the criteria is that the norms care about which order. All right, so that's the first selection criteria and the second one is asking whether the concentration in there. So if you expand or shrink the order set then that changes the subpopulations we regenerate by this procedure. I did, how that relates to being able to discriminate between different sets of orders across different ranges of concentration in real life I think is difficult to predict but within our data sets these populations are fairly stable. Next slide, two after. So I've argued before that in order to represent the identity of an order you have to integrate segregated input channels from the olfactory bulk and that may suggest that the way we observe order coding in peer-reformed cortex is not observed as such in olfactory bulk output in micro and crafted cells. So we went back to a previously published data set which we looked at micro cells and did the same kinds of analysis to see whether there's concentration in there and subnetworks already at the input level of olfactory cortex and what you see is two things. So first of all we see fewer concentration in variant norms involved than we see in peer-reformed but more relevant is what Renke just suggested that when we do a shuffle control that is we randomize the cell identities so as a reference for the numbers of concentration in variant norms you would predict simply from the statistical distribution of the data set then what we observe in the olfactory bulk is that the observed value is within that range of noise whereas in peer-reformed cortex it's very significantly shifted to the right suggesting that the segregation into concentration in variant norms is something that is if not generated at least strongly enhanced in olfactory cortex with respect to its olfactory bulk inputs. So to summarize this set of experiments I've shown you that the identity of orders is encoded in distributed ensembles of peer-reformed norms that identity independent of intensity is encoded in subnetwork on a subpopulation of peer-reformed norms and that this concentration in variant subnetwork may be an emergent property of olfactory cortex and not as such observed in olfactory bulk. And I think more generally moving forward we would like to propose that distinct subpopulations of peer-reformed norms can be identified or encode different features of an olfactory stimulus that may be order identity, intensity, perhaps valence and other things. So these experiments like I said highlight some of the functional diversity of peer-reformed norms in the second part of my talk I'll come to the molecular diversity of cell type and diversity in cell type identities we can now assign to peer-reformed norms and this work is very much based on a lot of previous work and perhaps first defined by the just lab in the spinal cord where they identified in particular transcription factors which define the identity of a norm and its connectivity with downstream targets. So these are again motor norms in the spinal cord and as you can see here that this distinct types of motor norms which innovate different muscles in our limbs can be delineated by their distinct patterns of gene expression and often combinatorial patterns of transcription factor gene expression. In the neocortex similar experiments have been described by Maklis lab, Ninazistan, Rubenstein lab and others such that genes can identify or sort of reflect based signal circuit organization for example the laminar organization of the neocortex so Cox one is a marker for the superficial layer to three cells while TLE four is a marker for deep layer five, six cells in neocortex and moreover more recent experiments have shown that again combinations of transcription factors can not only tell you about the organization of neurons into the different laminar of neocortex but also tell you about their connectivity so if you have Cox one neuron you are likely to project to the controlateral in motor cortex, you're likely to project to controlateral motor cortex whereas if you have TLE four neuron you project to sub-survival targets including the thalamus and the corticospinal tract. So we figured that having these types of molecular markers that can identify the connectivity of different piriform neurons would be a big advantage to have in piriform so what we did is we cut out the layers with deep sequence and from these deep sequencing experiments we identified candidate genes which we tested by in-situ and antibody staining so these are just a few examples of genes that are selectively expressed in a particular layer so for example PRDM-8, PDPD-3 are exclusively expressed in layer 2 not in 1 and 3 I should mention this is a nisselstain just as a reference for layer 1, 2 and 3 and we find genes that are expressed are specific for sub-layers for example F2 is expressed in these superficial layer 2 cells while MPCD for example is excluded from the superficial layer of layer 2 but expressed in subset of 2B and 3 etc. For some of these antibodies for some of these genes with antibodies so here are three more examples Wielin as Charles Greer has pointed out is fairly specific for excitatory neurons in layer 2A it's also expressed in some internal neurons in 1 and 3 Cox 1 is not present from this layer 2A but it's present in a large population of deep piriform neurons and we have several markers that identify a layer specific subset such as this one barred cell 1 so these are nice genes to identify types of neurons and look at the organization in layers doesn't tell us anything about connectivity yet so in order to get there we re-validated some of the piriform target areas by simply injecting an AAV channel YFP in piriform neurons so channel YFP is very efficiently expressed not some termini and then cut the brain from anterior to posterior see that piriform neurons project to the olfactory bulb this is what Florian just talked about in his previous talk in the previous talk they project to many other cortical areas and so we particularly looked at the medial prefrontal cortex at the cortical amygdala and at the antiviral cortex and that is because they are far apart and so we can now use retrograde tracing experiments to see how neurons projecting from piriform to these target areas are organized within piriform so that's such an experiment where we use colatoxin B as a retrograde tracer injected in bulb prefrontal amygdala and antiviral cortex and what you see immediately and I think what you can appreciate quite readily is that these neurons in piriform projecting to these different target areas now line up in different layers and not so different from the layers of gene expression patterns I showed you before so for example bulb neurons are deep neurons they're excluded from layer to A the frontal neurons are primarily present in 2B in contrast cortical amygdala and antiviral cortex are fairly excluded from deep layers but present primarily in superficial layer too so in the following experiments I'll try to convince you that the genes and connections match we did that in three different scenarios so first we ask whether genes that specify different layers or cell types in different layers specify the same cell types that are segregated in terms of projection patterns in other words are the cox1 neurons in deep layers the same neurons that project to the bulb and are the real in 2A neurons the same neurons that project to the cortical amygdala and the short answer is yes so about 80-85% of all cox neurons do project to the olfactory bulb so they're co-labeled by retrograde phases from the olfactory bulb with the cox1 transcription factor and they never express real in in contrast all the real in 80-85% of the real in neurons project to the cortical amygdala and cortical amygdala projecting neurons and never cox1 post so neurons in different layers match up well with transcription factor profiles that are layer specific we can push this one step further in fact we can also characterize these neurons morphologically by now sparsely label them with a retrograde the transported virus so we can inject the calf to Cree with a conditional morphological marker and peer reform and we see that these cox1 positive bulb projecting neurons are constituted by a fairly diverse set of pyramidal cells while the cortical amygdala projecting neurons are exclusively these semi-lunar cells which are characterized by the lack of basal dendrites so we can push this matching of genes and connections one step further and we can ask whether neurons that sit in the same territory but project to different target areas can be discriminated using the genes we look at so that's for example the case of bulb and prefrontal cortex projecting neurons they largely overlap in this layer to be of peer-reformed cortex so we can ask can we find molecular signatures for neurons that sit or occupy overlapping territories but project to different target areas and the answer is yes so the combination of two transcription factors cox1 and CTIP gives us a good prediction for the connectivity of patterns of these neurons so this is the overall expression patterns cox1 is in deep layers in peer-reformed CTIP is primarily in these superficial cells but they do overlap if we zoom in to layer 2B where these neurons sit then we see cells that express either CTIP alone in red cox1 alone in green or cox1 CTIP double positive cells which are shown in yellow and if we combine these molecular markers with tracing studies we find the following distribution the bulb projecting neurons summarized in these pie charts are either cox1 positive alone in green or cox1 CTIP positive in yellow there's very few CTIP-only cells in red in contrast prefrontal neurons again in the same area within peer-reformed are either CTIP-only or CTIP-cox1 but they're never green alone so they're never cox1 alone and if we now inject two different color retrograde faces in prefrontal and non-factory bulb we can identify neurons that project to both areas so that they bifurcate and project to both target areas and all of these neurons are both cox1 and CTIP so these experiments identify three types of neurons cox1 neurons that project to the bulb CTIP neurons that project to prefrontal cortex and cox1 CTIP double positive neurons which co-project to both target areas so these data suggest that we have molecular markers that can identify the connectivity patterns of neurons that are either segregated in layers or overlapping within a layer and so the last experiment in this context we did is we asked whether these molecular signatures of connectivity hold in the absence of all layers if we scramble the organization of prefrontal cortex and that's an experiment that was done 50 years ago by the characterization of these real amutin mice which have massive defects in the lamination of neoportex which is similar defects in the lamination of prefrontal so you see that in the density of the neurons you cannot detect any lamination based on the density of neurons real expression is lost due to the mutation of the real and locus however all the other genes that we've looked at in terms of layer specific markers remain to be expressed at numbers that are fairly similar to control only that they are now distributed throughout the prefrontal cortex so for example cox1 which is a marker for deep cells is now found without any bias across the entire depths of pierform so we can ask our connections to maintain in the first place we focused on pierform connections to bulb and the cortical mucular that's because these structures are reasonably well maintained in the real amutin mouse and we see that pierform neurons do project to the bulb and to the cortical mucular at numbers that are fairly similar to controls only again that we lose the lamina segregation and finally we can ask whether the markers we identify as delineating the connectivity patterns of these neurons are maintained in this scenario and the answer is yes so despite the fact that cox1 neurons are now positioned without preference across the depth of pierform 85% of cox1 neurons do project to the bulb very similar to what we see in controls and the real in cells so we cannot use real in as a marker for these superficial cells but we can use FETSF2 which overlaps with real in these semilunar cells and despite the fact that they are distributed or scrambled throughout pierform depth all of these or 85% of these cells still maintain the specific connections with the cortical amucular so to summarize this set of data we've identified using this laser capture deep sequencing approach we've identified genes that delineate distinct pierform layers and cell types these genes either alone or in combination can tell us about the specificity of pierform projection patterns and connectivity and this link between the molecular identity of neurons and their connectivity is maintained in the scrambled cortex of a real mutant animal which suggests or which sort of highlights the importance of intrinsic genetic programs in specifying connectivity rather than sort of local spatial information Do these different things? Yes, so I think by and large that's what we're doing now we're not specifically looking at this set of neurons but the hypothesis is that different types of neurons do different things and so the goal is to match up identity and connectivity with the functional properties of these neurons we don't have a lot of data yet but that's where we're going Right, so in fact maybe I can ask that in a minute it will come to that Okay, what happens to other transcription? Right, so the problem there is that these transcription factors tend to be expressed along the entire pathway so starting in the sensory neuron and the bulb in different subsets of bulb neurons I think we'd have to aim at conditional knockouts in piriform which is a hard thing to do Right, so we use viruses a lot It's... Yes, so it's a large area to manipulate with the virus So we are both... So from this deep sequence in there we have some candidate genes that the promoters that appear from specific and we are trying to generate free lines to see if they'll be useful for that purpose We don't have any yet We're hoping that other people generate them But in fact I'll go to the next slide in terms of understanding the genetics of the system a little better So quickly, future ongoing experiments and future perspective and the first thing I really would like to point out is sort of striking observations we made when we looked at gene expression patterns in piriform and each time you look you obviously have the neocortex on the hippocampus side by side and the prediction could have been that piriform is a simple paleocortex only contains three layers and maybe a fewer genes or fewer genetically defined cell types in piriform than you have in the six-layered neocortex Now that, at least for us, is very obviously not the case Every single gene that people have looked at in neocortex is a gene that defines the identities and connectivity of neocortical neurons is expressed in piriform cortex However, the basic organization of these genes is very, very different and so that's illustrated here in this slide So while Cux1 is a marker for superficial neurons it's clearly a marker for deep neurons in piriform and while CTIP is a marker for deep neurons in neocortex it's clearly a marker for superficial neurons in piriform This is not always the case we get all kinds of combinations it makes no sense to us What is also striking is that the genes that are never co-expressed in neocortex are very happily co-expressed in piriform and this is important because people have postulated that sort of cross-repressive networks specify these neurons in neocortex and clearly the situation is very different in the piriform cortex So, however, one you know, this apparent inversion of gene expression patterns these layers reflect the sequential generation of neurons during development and the observation that some of these genes are somewhat upside down in piriform suggested to us the idea that piriform is developed in a very different way and so we did an experiment that is identical to what Charlie described in the first day of the meeting Yes, we don't In fact, yes, so in fact that's a good so in fact we do now so in sections this is very painful because everything you want to look at ends up not being on your section so we're doing everything in cleared brains now where we, you know, particular any sort of transition areas a bit puzzling to us how do you, you know, make things connect from one area to another in terms of gene expression patterns So we did EDU birth dating experiments and what we see is what Charlie presented is that in contrast to neocortex at least piriform layer two develops outside DNA as opposed to inside out so in neocortex the early born neurons inhabit the deep layers in piriform you see that the early born neurons here indicated by EDU labeling at 11.5 are the superficial cells quantified here whereas the later born neurons in the 14.5 are clearly excluded from the more superficial layers and are predominantly present in the deep layers so in some way despite the fact that we have the same if not the same largely overlapping sets of genes that specify these neurons in piriform and neocortex the logic of circuit assembly appears to be fairly different and so what we're doing now is we're using the feds of two gene as an entry point in studying that so feds of two is a key determinant of deep layer cells in the neocortex as primarily shown by the nazi stance lab so it's essential for the specification of corticospinal tract neurons which also has big implications for mammalian evolution et cetera in contrast we see feds of two very robustly expressed in the superficial care from neurons that are very different in terms of the morphological characteristic intrinsic properties, connectivity, et cetera so what we're doing is we're following now using transcriptomics and enhancer accessibility studies the specification of these feds of two lineages to try and sort of identify key decision points in the specification of different cortical neural cell types that may also determine the connectivity and intrinsic properties and I think it will be important to sort of understand how basic neural circuit motifs are specified genetically what we also hope to generate by doing these experiments is more specific markers for peripheral neurons and that's sort of in response to Linda's question before that will allow us to target these cells in a more refined way so the other sets of experiments we're currently doing is bringing together and that's what Pierre-Marie pointed out the genetic and imaging and behavioral tools eventually with the idea in mind that different types of neurons do different things it's somewhat trivial but it's not a very prominent concept or hasn't been a very prominent concept in the field so we can target these different types of neurons now using mass genetics we can use imaging to assess the functional properties and optogenetics and chemogenetics to manipulate their activity we are also particularly interested in how information is being transmitted throughout the nervous system and that's again very similar to what Florian discussed with the idea in mind that different features of information are not transmitted randomly throughout the entire cortex and that they may be used in differential ways depending on the behavioral context and we can target so we can do that by targeting neurons based on their connectivity patterns using retrogradely transported viruses and finally we can do that in a way behaving animals so this takes a lot of weight off my shoulders by either by using Greenland's technology both in these miniscope types of experiments but also in two photon head fixed experiments and so the idea is to understand how different types of neurons, how circuit functions as I pointed out in the introduction emerge from the concerted activity of different types of neurons and how information about the stimulus about all the identity, intensity, valence, et cetera is being routed throughout the nervous system in a behaviorally dependent or behavioral context dependent with this I'll stop and I'll acknowledge the people so the genetic work was done by a student of the ODATU who was in fact a student here at CISA before she joined my lab imaging experiments were done by Benjamin Roulin in my lab and a lot of the, this was done in close collaboration with Kevin Frank said Duke was done electro-extracellular recordings and come to somewhat similar yet complementary conclusions we got a lot of help from BISPA TV in terms of data analysis Andreas Schaefer, Gloria Toy and Sonia Garell for the molecular studies and this is our funding and thank you very much for your time. Thank you. Thank you.


All right, welcome, everyone, to today's Google Webmaster Central Office Hours Hangouts. My name is John Mueller. I'm a Webmaster Trends Analyst here at Google in Switzerland. And part of what we do is Webmaster Hangouts, together with publishers and webmasters from around the world. As always, I'd like to give those of you who are kind of new to these Hangouts as a chance to ask the first questions. Is there anything on your mind that we should start off with? I have a question if nobody minds. Go for it. I'm a YouTube pop contributor at the YouTube forums and for the Brazilian market, for the Brazilian users. And I've been lately thinking about working on developing some content for the market of Brazil on the website. And my question is, since there is so much related content on the web already, what can I use as a reference material to help me make quality content? I mean, what can you share to help me distinguish that if I want to make quality content? Is there information that I can find that can help me sort of guide me to develop good quality content that doesn't duplicate? It doesn't seem like I'm just retyping this information because I'm trying to help the users that with me work on the Brazilian YouTube form for the top contributors program. So it's like more of a Google-focused product, but I don't want to seem like to duplicate them. I think you're totally on the right track. That sounds like a good idea. And it sounds like you have the right mindset there. So I wouldn't worry too much about finding documentation that tells you how to write good content. So it sounds like you're not rewriting content. You're not just creating something for the sake of putting something online. So that sounds like a good idea. And what I would recommend doing there is also making sure that you always have that feedback loop from your users, that you have a chance to hear from them and say, is this the right thing? Am I doing the right kind of content that you all like? Or is this something that you think is terrible or boring? Kind of like you would have on YouTube where you have the comments below the videos, those kind of things. OK, so good. Thank you. All right, more questions from any of you others who are kind of new here. I see a lot of new faces, which is awesome. Yeah, feel free to unmute or jump on in. Otherwise, I'll just run through some of the questions that were submitted so far, and we can see how that goes. Let me just mute some of you, because there seems to be a bit of noise in the background. I'm not sure where that's coming from. If you want to jump in in between with comments or questions, feel free to unmute. All right. So we're starting off with a simple question about mobile indexing, which is probably not so simple after all. We currently use dynamic serving for the mobile theme on the same URLs as desktop, but we're moving to a PWA to replace our mobile theme. Due to technical limitations, we can't use the PWA on the same URLs as the desktop theme, so we'll be launching it on an m.subdomain. Are there any things we need to be careful about? Essentially, the main things to watch out for there are just the same as with any mobile site, so it's not specific to PWA. In particular, we need to have that connection between the desktop pages individually and the mobile pages, so the link with the rel alternate from the desktop and the link with the rel canonical back from the mobile pages. For PWA, this means that we need to be able to crawl and render the mobile pages as well, so I would double-check that with Fetch as Google so that we can actually pick out that link back to the desktop pages. And with that, we should be able to recognize that this is your desktop site, this is your mobile version of that site, and swap out the URLs on demand when users search on mobile devices. The second question kind of goes into the same kind of topic with the mobile-first index. What about the rel canonical and rel alternate tags? This stays the same, essentially like we have it documented where we have the rel alternate tags from the desktop pages to the mobile versions and the mobile version, when we render that page with the PWA, we would probably need to render it to actually see all of the content. We'd need to see the rel canonical link back to the desktop page. And with that, we can understand this connection between this is the desktop page, this is the mobile page, and for mobile-first indexing, we would just index the mobile version of the page. Hey, John. Hi. Hi, it's Max here. You just answered my question. Oh, awesome. If we go back to the first part of the question, where we're moving, we'll be moving from dynamic serving to the PWA on separate URLs, will there be a kind of migration process where, because the traffic for the mobile has been going to a single URL, will we expect to see some kind of fluctuations while the traffic is moving over to our new mobile domain? Probably not so much, especially with the mobile version, since that's not the one that we use for indexing. You probably wouldn't see such strong or visible fluctuations in search because of that change. So what might happen is that it'll take a while for us to understand the connection between the mobile and the desktop pages, so for us to show the mobile URLs in the search results. But the ranking and the indexing should remain the same because we have the desktop version that stays the same for crawling, indexing, and ranking. So that's kind of an easier change than if you change the desktop site or move the desktop site to different URLs. OK, thanks. And just another question with point two and my question with the canonical links and the rel-alternat, will they always stay that way in the future? We won't have to switch the alternate to the desktop and the canonicals to the mobile. I don't know. I can't make any promises for always in the future. I suspect at some point there will be differences. But at least our plan with mobile first indexing is to make it as easy as possible, which means that we kind of try to handle that as much as possible for sites. So we don't want sites to kind of have to change things around because even adding a simple meta tag is sometimes something that takes a lot of time and we understand that. And doing something like changing connections between pages takes even longer because you have to try to get that right. So that's something where we're saying we're going to try to take the existing markup that you have on your pages and just use that for mobile first indexing. OK, that's great. Thanks, John. Sure. All right, off to a question about internal links. If you have two internal links on the same page but with different anchor text and these are pointing to the same destination internal page, would Google use or give preference to the first anchor on the page or distribute the weight equally between the two? How does that work? What can we do to make internal links as efficient as possible? So I guess there are two aspects here. On the one hand, you could probably work out what the internal implementation on Google side is at the moment for something like this. On the other hand, our general recommendation is to just make sites that work well for users. And that's something where we constantly change our internal implementations to try to figure out what do we need to do on our side to understand what a normal website looks like. So if you're creating a normal website and you have multiple internal links going to the same page with different anchor text, then that's something that we should be able to handle fairly well. Without you having to artificially think about which link is the first one that I need to focus on or that I need to tweak, that kind of doesn't really make sense for us. So in principle, when you take a step back, our goal is to be able to understand natural websites. So if you create a natural website, then that should just work on our side. We're redesigning our branch pages. Can the length of a page ever be seen as negative as our site template is A4 with, as opposed to many sites that use the whole screen as with, thus allowing to get more information on a page without having to scroll down or reduce information in tabs? Any kind of question with ever or always is really kind of tricky for me to answer. From my point of view, I don't see this as being a problem at all. So if you create a page that's more longer or one that's kind of like with the condensed information on the full width of a page, that's really totally up to you. And especially on mobile, all of that changes anyway. So that's something where I would focus on usability and making something that works for your users and not worry so much about how Google actually picks up that content. We've seen some sites that have really long pages that perform really well on Google. We've seen other sites that have fairly short pages and more pages that perform really well on Google. That's kind of up to you. That's something where I'd recommend you try things out, see what works well for your users, and focus on that. We know about a site that has scraped our content. That site is a doorway site, and they're spreading malware, and they're bad. We're trying to fill out the DMCA claims against them, but with no luck, it seems that for some search queries, Google shows their results instead of ours. What can we do about that? So in general, the DMCA process is probably the right thing to do there. This is a legal process, and I can't give you legal advice, so I can't tell you if it's exactly the right thing to do there. But you can definitely check in with a lawyer and look at that process and see if that applies here. In general, this is something that you can do. You can submit to both Google and to the website hoster to kind of have them take action on that. The important part there, especially when it comes to Google, is that this is a per page setup. It's not something where you can say, this whole site is scraping mine, but rather you'd have to say, well, this individual page and this individual page is a copy of this individual page or that individual page on my site. And then that would be something that Google's legal team would be able to process and perhaps take action on if that's appropriate. So that's kind of what I would aim for there. There is no kind of like backdoor system on Google's site where you'd be able to contact someone from Google's search team and say, hey, this site is copying mine. I can't get the DMCA to work. Can you just take it out for me anyway? That's not what we would do. Sometimes when I want to go to a site that I like, I type the URL in the Chrome address bar directly and don't use Google. Can you see this direct URL type in and say, hey, this site must be awesome? No. That's generally not something that we would see. And as far as I know, I don't think we would use that for search at all. So that's something where sometimes, depending on the settings that you have in Chrome, it might be that they log this for diagnostics purposes. But as far as I know, that's not something that we would use at all in Chrome. If you think this is a really awesome site, then in general, we try to collect other signals as well that tell us this is a really awesome site, rather than just individual people that happen to type a URL into the Chrome address bar. Especially on mobile, typing things into your address bar is really painful. So I don't think that would be something that would be that useful for us. We recently migrated domains from a.net.au site to a.com.au website. And in the process experience, an extreme drop-off inside traffic. Is there any way to see if our value has been retained? So in general, if you do a site move, which would be something like this, I'd recommend you follow the steps that we have in the Help Center with regards to setting up redirects properly, making sure that everything cleanly redirects on a per URL basis. And in general, that's something that should work out really fairly well. So it doesn't really matter so much from where to where you're moving. In this case, you're moving between two country code specific top-level domains, which is totally fine. This means that geo-targeting will generally be the same. You don't have to change any settings in Search Console. So that's something that, in general, we will be able to forward fairly easily. What might be happening here is that, perhaps, in general, Google has just decided, or rather, its algorithms have decided to reevaluate your website. And that might not be related to your site move at all. It might just be that this kind of reevaluation would have happened regardless of where your website is hosted. So that's one thing that might also be happening there. What you could do to try to figure that out is to see when exactly these changes happened in Search, was it really right when you did the site move or was it somewhere before or after that site move where you started seeing this change in Search? And depending on that, that might be something where you'd be able to say, perhaps there is a technical issue with the site move, which you would probably be able to see, or perhaps it's more something that Google is generally just trying to reevaluate my website overall. And that might be a sign that you should, perhaps, take a step back and think about quality and think about what you could do to significantly improve the quality of your website overall. If you're totally unsure, like which direction this would be headed, I'd recommend going to the Webmaster Help Forum and getting advice from other people there who have done similar moves or who have experienced kind of diagnosing similar kinds of issues across different types of websites. Is it a problem if we 302 all non-mobile users from an AMP page to its desktop canonical? I personally don't like that, but the dev thinks it's cool to do. We're also redirecting Googlebot non-mobile traffic as it's not a mobile user agent. I don't know what would actually happen there. So with regards to what users do, that's kind of up to you. The thing to keep in mind there is that if this AMP page is being shown in the search results with the AMP viewer, then that would be on the cached version of the AMP page. It wouldn't be on your server itself. So that wouldn't be something where you'd be able to do this kind of redirect on your site. On other hand, if people are going to your AMP pages because they found a link there and this is on the AMP page itself on your website, then that's kind of up to you. With regards to Googlebot traffic, I don't actually know for sure which types of Googlebot would be expecting to see the AMP content there to be able to confirm that this is actually an AMP page. It might be that we're also crawling AMP pages with the traditional Googlebot, which isn't really like desktop or mobile specified. And if you're redirecting that Googlebot as well, it might be that we wouldn't be able to pick up those AMP pages properly for search. But that's something you could double check on your site. Maybe just take a handful of URLs and set up this kind of redirect and see how that works out for you. And if these pages continue to be shown as AMP's in search for mobile users, then probably that works out. I suspect the setup where you're redirecting Googlebot as well might be a tricky one. So that's one thing I kind of watch out for. And I kind of assume that this is something that could change over time as well because it's not really a defined state. How does Google treat the acrylics in text on a page or in title tags? We try to treat characters the way that they come. So this is particularly if you have kind of these accent marks on characters or kind of variations of characters that were there multiple versions that are sometimes used. In practice, what happens here is we try to understand which words are synonyms of each other. And we try to do that in an algorithmic way. So it's not that we have any linguistical models built into search that say, oh, this character maps to this one. And therefore, all words that use this character can also be found like this. But rather, we try to recognize which words have synonyms based on what we see people searching for. And based on that, we'll try to pick that up and show that in the search results itself. So what I would do in a case like this, if you have these characters in your language on your pages, I would just write naturally. And just write them the way that they're normally used in your area and in practice, that should just work out. We have a child care business with five locations in Houston. Our website has the Locations page with all five locations listed. Do you recommend having individual pages for each location to rank better? The content would be the same on all five pages. So I think with five individual pages, you could go either way. It might make sense to have individual pages, especially if you have unique information for each individual location. That could be things like your employees in those locations, opening hours, or something that's kind of unique to each of these locations. Those would be the kind of things that I would perhaps list on these type of pages. If you don't want to do that, then probably one page with those five locations listed on that would work just as well. Essentially, this is kind of up to you. Sometimes it means more work to create more pages. Sometimes it means better targeted users going through those pages. That's kind of hard to guess from my side. With regards to the second part of the question, saying that content would be the same on all five pages, if the content is actually the same across these five pages, then I suspect you won't get that much value out of having separate pages there. But again, with five pages or five locations, it's such a small number that from our point of view, we wouldn't see this as a doorway site. We wouldn't see this as being problematic. It's really more up to you what you'd like to put on your website. Our site used to be on the top of Google, but for a year now it continues to go down. It has reached the seventh and eighth page. We didn't do any blackhead SEO. We don't have server issues, nothing unusual. What could be the reason? In practice, this is something that can happen all the time. So algorithms can change. Our evaluation of your pages can change over time. It can be that the rest of the web changes as well. So just because you're not doing anything explicitly wrong doesn't necessarily mean that your website will always be ranking at exactly the same place forever. So this is something where if you're seeing changes like this, I'd recommend kind of taking a step back and thinking about what you could be doing on your site that is significantly better than all of the others that are kind of ranking for these kind of queries. So don't try to be just as good as the others. Don't try to just say, well, my website has been like this for the past 10 years. I'll never change it. It's always been good. But rather think about what you could do to kind of significantly move things forward. As an example, on our sites, we constantly do experimentation to figure out, are we making the right assumptions? Are we still doing the right things? So for instance, if you go into Google Search, you will almost always be in multiple experiments where we're constantly testing things and constantly trying new things out to figure out what we need to change to continue to evolve. So these are things that I would recommend doing rather than just saying, well, my website has been like this. And I haven't changed anything. Therefore, it should continue to be ranking or continue to be as relevant as this. How come a home page still indexed in Google and ranking for numerous queries is not indexed anymore on the first keyword. It was first indexed for on the first page of Google? This is kind of the same thing. Rankings can change. The rest of the web can change. It's normal to see fluctuations and changes over time. How can we see which URLs in Google have been indexed so far? If we submit a sitemap in Search Console, Google will say 95 out of 100 are indexed, but which of those five are not indexed. So there is no way to get a list of the indexed URLs at the moment. What you can do is split your sitemap up into smaller parts and kind of look at it that way. In general, however, I wouldn't focus so much on trying to get a high number of URLs indexed, but rather focus on making sure that that which is shown in Google is actually relevant and useful for users and for yourself. So in practice, when we look at most websites, for example, if we look at the data shown in Search Analytics, you'll see that for most sites, there is only a handful of pages that is actually shown in the search results. So getting more pages indexed doesn't necessarily mean that you'll be more visible in Search or that you'll get more traffic. So I would focus more on making sure that what you are providing on your site is relevant to users. And in turn, we'll try to recognize that and index more of those kind of pages. I got a Search Console security warning for one of our sites. Without further explanation, how can I find out what the problem might be, I would recommend going to the Webmaster Help forums for something like that. The folks there are extremely good at helping with security issues and trying to kind of analyze what might be going wrong, what you could be doing a bit differently. Why is the organic session count in Google Analytics app indexing data so drastically different from the clicks in Search Console data? I don't know. So specifically, I don't know exactly what you're looking at there with regards to the app indexing data. In practice, Google Analytics tracks things quite differently than Search Console. So Search Console will track kind of the traffic from someone searching to clicking to your website. And Analytics tracks the other half. So kind of the part when someone is on your site, or in this case, within your app and from there. I don't know what specifically you're looking at with regards to app indexing and Analytics because there are different ways of setting that up and of tracking kind of the user data within Analytics for apps specifically. There are some questions about people trying to jump in the Hangout. So for what it's worth, there are 10 slots that are available in the Hangout. And when they're taken up, you can't really get in unless someone leaves again. So that might be one of the problems there. The link to the Hangouts, I usually post in the thread for that Hangout in Google+. We know that Google recommends responsiveness, but what's the take on dynamic serving if the URL stays the same? So essentially, I guess the question of responsive design or dynamic serving, which one of these is better. So responsive design means that, OK, I'm on my back. All right. Wow. Glad that came back. OK. So dynamic serving, responsive design, again. So with dynamic serving, the tricky part is that since you serve different content, it might be that Googlebot on mobile doesn't see the full content. So when we shift to mobile indexing, that could mean that we're seeing slightly different content or simplified content compared to what you have on your desktop site, which could mean that we have less to work on for indexing. So in particular, things like meta tags or images or videos on pages or even the textual content on the page, that might be something that is perhaps not as optimal on your dynamic version if you're not watching out. So this is definitely something you can do really well with dynamic serving. There are lots of sites that use dynamic serving and do it in a really fantastic way, but definitely something worth watching out for. With responsive design, you don't have that as much of a problem because the HTML is the same. So all of the links, the images, the metadata, all of that is already on those pages. So with dynamic serving, you just need to make sure that you're really providing the full content as well. I live in Norway. I write in Norwegian. When you do changes in the algorithm, when are those changes rolled out to other languages, other than English? Is that instantly, or is there a waiting period? So I am in Switzerland. We have the same worries. In general, when we make algorithms for search, we try to make them such that they're valid across the board, across all types of websites, regardless of the language, regardless of the font that's used, the characters that you use to write. We try to make those changes as universal as possible. That's essentially the best way to work with the whole web, because the web is very diverse. There are lots of different languages out there. There's lots of content in non-English out there. And we need to make sure that any search-related change that we make across this vast collection of content is valid and useful across the board. So as much as possible, we try to make sure that these changes are rolled out to all languages all the time. There is one kind of traditional exception there, which comes with regards to things like rich snippets, structured data, the knowledge graph information, kind of the business-related information that we show in search, things like the connections, also with streaming services, where we maybe show a link to a streaming service that provides the content that you're looking for. Those kind of things are sometimes a bit trickier for policy or for legal reasons that we can't roll them out in all countries all the time. So sometimes there are issues there with regards to specific search features that just take a bit of time to roll out everywhere. And often that means we roll them out in the US first. Sometimes we roll things out in other languages first as well. But these are the kind of things that I don't see all the time in Switzerland. You probably don't see all the time in Norway as well. When you look at our blogs specifically around structured data, there are probably things there that say, well, we're rolling this out in the US now. And depending on how that works, we'll work on getting it to all other countries as well. Why do error reports take so long to update? Good question. So I assume you mean search console, like the crawl errors, those kind of reports. The tricky part there is we can't crawl the whole website all the time. So we have to take an incremental approach and crawl things step by step, which means we will see some errors fairly quickly. And some errors will take a bit longer to see. And similarly, we'll be able to kind of resolve some errors fairly quickly because we've reprawled them and seen that the error is gone. And for other errors, it just takes a lot of time for them to update. So this is something that crawling and indexing can go anywhere from a couple of seconds or minutes even to a couple of days to a couple of months. It could be even up to a year for us to kind of re-crawl and reprocess individual URLs. So if you have a site-wide crawl error or some other kind of issue across your whole website, then you'll generally see that the more commonly crawl pages kind of get cleaned up fairly quickly when we re-crawl them and see the error is gone. And the rest of your website will take quite some time for us to actually re-crawl and reprocess all of that. So it's not so much that Search Console is saying, oh, I am too bored to actually look at your website and look at your errors. It's more that we don't want to overload your server. And therefore, for technical reasons, we can't re-crawl everything immediately. So it's just going to take a bit of time. In practice, what also happens, a slight effect there, is when we see bigger site-wide changes across a website, we will try to re-crawl that a little bit faster than we normally would, just to make sure that we're able to kind of catch up with the important pages a little bit faster. I'm SEO manager in one of the first three agencies in the MENA region. Let's see. I'm faced with an issue that I haven't seen before. Have you seen a website that ranks on almost all regions generic and long-tail keywords except for the targeted region? For example, SEO services Dubai is ranked second on .com.sa and six on .com while it's ranked on page 16 in our target area. What can we do? So it's kind of hard to say what specifically you're doing wrong there. I don't know which website this is. But in general, we don't have algorithms that try to kind of hide a website in its target area. So that's not something that we would be doing there. It might be that we're having trouble understanding the geo-targeting of this website. So that's something that might be happening there. I don't know if this is the case, but it might be that there are things like links that could be causing a problem here, too, with regards to especially when you're looking at an SEO site that maybe you've been building a lot of kind of weird links that are hard for us to understand that they actually belong to your region, that could be playing a kind of rule there as well. But this is something where I almost recommend posting in the Webmaster Help Forum to try to get some more advice there. My feeling is that this is not something where our algorithms are doing something explicitly against your website, but rather they're just like confusing signals probably for your website that make it hard for us to understand what it is that you're actually trying to target. I'm trying to replicate an experiment here. So he links to a page about AJAX and SEO, there's Google Index AJAX content, and I think it goes on in that I insert links with JavaScript into a page, and I can't see that Googlebot is actually crawling and indexing those link pages. Will that be a problem? So the tricky part here is kind of that this is not really something unique to JavaScript. If you set up a random test site and you have links in there, then in general our systems are going to recognize that this is some random site, then it's not worthwhile to crawl everything that we see there. So that's probably something where it's less a matter of the technology that you're using to kind of test this, but indexing anything that we find there either. So that's probably what you're running into there. In practice, if you're creating a website with a JavaScript framework, if you're using React or Angular or anything like that, and you use normal A elements for links between your pages and those links point to actual URLs that we can crawl and index or render at least, then that should work out just fine.  So that's not something where you'd need to kind of artificially set things up. One thing we do recommend is to use something called Isomorphic JavaScript or on Angular, it's Universal Angular, I think, where essentially you pre-render the first page that any user sees and you provide the raw HTML for that user. That has the effect that for users, these pages load really, really quickly because they don't have to do all of this JavaScript to actually build up the page. And for search engines and other kind of browsers or user agents that access website content, such as social media sites, they see the full HTML as well. And essentially, they don't have to do any of the JavaScript processing either. So if you use something like that, then you kind of have the best of both worlds. You have the fast development times from a modern web framework, and you still don't have to worry about anything related to search because you're essentially providing a static page to search engines. I have a client that uses a tracking tool to see how they're ranking for specific keywords. Search Console doesn't give us this information. Are we violating Google Webmaster terms of services on automated queries? Yes, probably. So a lot of these search results tracking tools, they scrape our search results against our terms of service, against our robots text. And that's something that would be, in general, violating our terms of service. So that's not something that we would recommend doing. It doesn't matter so much which tool you're using, but if you're scraping our search results, then that's not really something that we like to see. On the one hand, we explicitly have robots text files set up for these kind of things.  We see a gigantic load from various tools that are scraping us on our servers, which makes it a lot harder for us to kind of provide that level of service that people actually expect from Google. And finally, the other thing to keep in mind is that if nobody is searching for these queries, then it's probably not so useful to track the ranking for those queries, because that has kind of no direct value there. So if people are searching for those queries, then Search Console will be showing that as clicks and impressions in Search Analytics. If nobody is searching for those queries, then it doesn't really make sense to track the ranking in those queries. It's like you're ranking for this query that nobody is actually searching for. That doesn't provide any value for your website. That doesn't provide any conversions. That doesn't bring you any customers. We noticed an increase in 500 server errors since March and can view the actual URLs listed in Search Console. They're mostly very old links. And it looks like the number is increasing further. Is there something like the most common reason for an increase in 500 errors? What's your recommendation for those? So 500 server errors are errors that we see from your server directly, which tell us that for some reason or another, this URL is causing an issue on your server. For the most part, that doesn't matter so much if this URL is not meant to be indexed, then an error is fine. On the other hand, our systems try to recognize an increase in 500 errors and try to assume that this increase is due to what they're doing, perhaps. So our crawling systems in particular will recognize a rise in server errors and assume that perhaps we're crawling too hard and will step back with the crawling. So that's something that I would watch out for there. If you're really seeing a change in the number of 500 errors on your site, then that would be something I try to take action on. So what I would recommend doing there is looking at the URLs that are listed in Search Console. And even if these are older URLs that are no longer valid, I'd make sure that your server returns a clear 404 or 410 result code telling us that this URL is invalid rather than returning a server error, which tells us maybe this is valid, maybe it isn't. I can't tell you because I can't process the rest of your request. So trying to have those URLs returned 404 or something similar would be my recommendation there.  Let me just pick a handful here to kind of go through. We've been hit with a penalty for spamming structured data. We tried to fix the problem. We looked at how other sites are implementing this, and they seem to be going even doing even worse. So what I would recommend doing there is posting in the Webmaster Help Forum.  In particular, I wouldn't look at how other people are doing this and saying, well, if they're getting away with this, then I can get away with this, but rather think about what you need to do to actually comply with our policies. In practice, what is also the case is that the structured data team, when they take action on a site, it just affects the rich snippets, which are similar. It doesn't change the ranking of a site. So this is something you can probably work on at your own pace. You don't really have to kind of rush through because the rest of your site is still being shown in Search Normally. So, John, this is my question. Oh, awesome. Yeah, so we've seen quite a dip in search traffic, actually. So it's been about 10% dip because we've lost our rich snippets, which, obviously, we've tried to go through reconsideration. And the first one, I think it took two days. The next one, it took a week. And now we're on to our third reconsideration request. And it's taken almost a month. Is there some sort of timeline for this? Sometimes it takes a bit longer, especially if things are going back and forth, then that can take a bit of time. Let me just double check. So it also looks like you might have had some issues with hacking. Is that possible? Yeah, so we had a hacking problem, I think, on our HTTP site, where we also got the spam instruction data penalty. But we saw it affect our wider site, which is our main site is HTTPS. So we're just trying to fix it across both of them. Let me just double check. Maybe we can take a quick look at this afterwards. Yeah, that would be a great idea. Yeah, maybe after we end the broadcast, I can take a quick look at this. But in general, this is something where usually the folks in the forum are really good at recognizing these type of issues. And they can guide you and say, hey, you're using reviews in a way that wouldn't be compliant with the policy guidelines. So I can double check what's kind of happening there. Maybe I can give you a bit more information. I don't know. But for the more general situation, if you're in something similar to this case, I'd recommend checking out the forum. Let me just double check the other questions that are still here. There's a quick question that I think we had briefly touched upon before we started. Can you confirm that these two things are not recommended by Google, building backlinks from articles and video submission sites? Yes, that's correct. That's not recommended. That sounds like a natural link building. And two, paying for Google Ads doesn't help improve your search rankings. That's also correct. That ads on Google, they don't affect the natural rankings of a site.  So maybe I can just switch over to live questions for the moment. And if your question is one of the ones that is still listed here that I haven't gotten to so far, feel free to copy it to one of the next hangouts. I'll be setting those up probably later today. Or, alternately, if you'd like to get an answer a bit faster, feel free to jump into the Webmaster Help forum for some advice there. All right. What else is on your mind? John, can I ask a question regarding the infamous sandbox? Over time, Google has been saying there is no such thing as sandbox. And on my part, trust me, I believe you. But I've been participating in many forums. I always see people saying, Google is lying. They are not telling us everything that really happens because they posted pages. And they take a long time to get ranked on the search results. But on the other hand, it's also not consistent. Because sometimes they see that some pages get ranked. And basically, what many people do also, those that do not believe, they start using Black Hat techniques to build links and such to rank their pages faster. And to a certain extent, it works, they say. And so my question would be, what can you tell to these people so they start believing Google and eventually stop resorting to Black Hat techniques and get their pages ranking faster? What they could be doing wrong so they don't get the pages ranked as fast as they will? That's a tricky question. It's kind of like, these people don't believe you. You should tell them that they should believe you. I don't know what to say. So if you don't want to believe our advice, then it's, yeah, I don't know. But I mean, it's completely normal that for some areas, it's not that trivial to get a new page into the search results. And that's kind of the normal way that things work. It doesn't mean that there is a sandbox or that there is anything crazy happening there. It doesn't mean you have to resort to Black Hat techniques to kind of get things in there. Chances are those Black Hat techniques will cause more problems for your site, then they'll actually provide value. So from my point of view, this isn't something that is black and white, where we'd say any new page that shows up will always be shown on the first page in search results for Google because that wouldn't make sense. If we have a lot of really good content available already, then of course, new pages are going to take some time to kind of build up the value that is comparable to the other sites that are out there. So there's no magic trick where I'd say you can get any page to rank on page one in Google for any keyword that you want. OK. Sometimes I go, you mentioned, just to finish this question, sometimes I go, you mentioned that for an existing site, when it publishes a new page, Google will somehow evaluate that the site has been publishing consistently good content and that eventually would benefit the site to be the new pages of that site to be taken more seriously or with more relevance. Is that a correct interpretation? Yeah, yeah. To some extent, that happens. When we see something completely new on a website and we don't really know how to judge that, we might kind of defer our decision until later when we have a bit more information. And in the meantime, take some of the signals that we do know about from this website into account. So that can definitely happen. Great, thanks. OK, good morning, John. Hi. Hi, how are you? And regarding to the question that my website is ranking almost all of the targeted countries except the targeted countries, the whole site is already CCTLDs, which is my country code. So there's nothing to manage when it comes to the target. But I'm not sure. I think it's kind of algorithmatic penalty. So I'm trying to figure out what is the exact problem that to avoid. The website is chain reaction to TAE. OK, we are facing this since almost two years. And I'm trying to fix it since a lot of time. I have joined many live sessions or even the Webmaster Center. Can you type the URL in the chat, maybe? Yes. I can't promise that I have an absolute answer for that. It sounds like something that's probably a bit trickier to resolve. So probably the best approach would be to kind of look into the Webmaster Help forums and try to get advice from other people that are in similar situations. And another aspect might also be that in the target market, maybe the competition for those keywords is just much harder than in other areas. So that's something where you would traditionally see differences in rankings as well. But I'm happy to take a look if you could post the URL in the chat. I have just posted to thank you very much. In the Hangout Chat or which chat? No, the Google Chat. Oh, OK. So that would probably be on my personal profile. So I have to kind of check that out separately afterwards. Yeah. OK. Sure. All right. Let's take a break here. I'll stop the broadcast, and we can take a look at the other sites afterwards as well. All right. Thank you all for joining in. I wish you all a great weekend. And maybe I'll see you all in one of the future Hangouts again. Thanks, everyone. Thanks, John. Bye-bye.


Yes, we're here. I'm Meredith Marachanitz alongside Clint Frazier. Clint, how are you doing?  You know, I just got home to Atlanta today. I've been spending the last couple weeks in Tampa with some of the guys that were still down there. And just trying to find things to do and a lot of things that we did were play Xbox and go to the field. I mean, it was very limited stuff, but we made the most of it while we could. Were there still a lot of guys that were working out there? There were a few.  So, you know, there was a large amount of people that showed their faces over the time being, but only a few would come in at a time. Was it odd? I know Marcus Tim said the other day that he's wearing gloves. Was it just odd the way that everything transpired and the social distancing, the way you guys had to try to work out? Yeah, it was weird, you know, because you started to see people take more precaution on things that they probably wouldn't. And for instance, like, you know, every day we have a couple of different BP throwers that throw throughout the day. So, you know, they started to be cautious of what baseballs they were throwing and one Ben seemed to be dedicated to one BP guy and stuff. And, you know, it was unique, but, you know, we still found a way to get the work that we needed done. And it was good.  And, you know, get the chance to be around guys like DJ LaMahue and Judge and Stan and then just really reap the benefits of the one on one or the smaller groups, the group settings to be able to get stuff done. Hey, you mentioned making the team. You were poised to probably make that roster on opening day this year. I imagine that's a tough pill to swallow. Obviously, this is all bigger than baseball or crazy things going on in the world right now.  Yeah, you know, I mean, I figured if I didn't make it, it would be caused by a player and not by a virus. So, you know, I'm still positive. I still think that I did some good things in spring training and, you know, obviously guys will have the chance to come back and be healthy whenever the season does start, if it starts. So, I'm just hoping that I put myself in a good enough position to be able to, you know, contribute more than I did last year, whatever that may be. Now, you mentioned the video games, and I know there is an intense Madden tournament going on right now spearheaded by Tommy Cainlake. How are you doing in the tournament? All right. So, last year was, it was, it was different. It was difficult, not last year, last season. So, I didn't have my PlayStation with me. So, I had got to pick a team that was drafted by the computer. And ultimately, I wanted the best quarterback and who better than Lamar Jackson. I took Lamar's team. It was not star studded by a lot of offensive threats. So, I've been joking around with a lot of guys in the group text and saying, you know, I sold my soul to the devil and sold everyone on my defense. There's no players on my defense left. I'm running the most powerful offense right now. I have the number one rated offense in the league, but almost the dead last rated defense.  I'm seven and one right now. I'm leading my division. And I think I got a chance to get a first round behind the playoffs this year, maybe upset Ben Heller in the first round. Exciting. We know Ben Heller and Tommy Cainlake went out for the championship last year. Are there any other ringers or any guys that are emerging as very good players in that Madden league? To be honest, like Ben is still like, all right, so Ben, Ben, somebody that you have to watch out for if you don't play your best game, he's going to embarrass you.  Like there could be six seconds left and that guy's still going to try to score. So those guys are the ones that you have to watch out for because it's hard to show up to the field the next day and look some of these players in the face and be like, yeah, like I got beat by 60 last night. Hey, one thing we've learned about you over the years, you love you some sneakers as do I. I set this up just for you, Clint, just for you. I had to put some of my selection out there. So do you have all your sneakers with you in Atlanta? Do you want to show me a couple of your favorite pairs? Yeah, you know, I will say that my favorite pairs aren't with me because they're they're on their way back from Tampa, but I still have, I still have a good collection sitting here but as far as my, my favorites go and my most expensive pairs they're not, they're not with me but maybe it's a blessing that I don't have to show up how much money I might have spent with you these pairs. It kind of turns into an addiction though, right? Once you start you're like, I need that pair. I need that pair. This pair goes with this outfit. I need this pair. It's shameful. I got a few for you here. I'll show you a few. Sweet. Nice. So, I mean obviously I just bought this house recently and I'm working on this shoe closet but I mean for the most part my best pair sitting here is probably, these are called the the off-white MCA They're made by Virgil Ablos. These are called the Grim Reaper Virgil Off-White Blazers. These are a hard pair to come by. Obviously they're pretty expensive which is why I probably shouldn't have worn them for the first time in the dugout in AAA this year. That probably would upset some people. All my feet right now I have the Travis Scott Lowe's. This is probably my favorite Lowe's. I like to wear the pink laces with them. I don't have any particular reason why. I just think it looks cool. Here's another pair. I mean this is another one of the harder ones that could come by. These are like the Miami based Jordan ones. So like inside of them they have 305 and an MIA. So it's just designed for the Miami Hurricanes but you know I don't have, like I said, I don't have every pair in here but I have some, I have some cool ones. I mean one of my favorite pairs are these. So if I have the other pair, okay here we go. So this pair is how this shoe starts. But if you take rubbing alcohol you can change it to that color. Oh wow that's pretty cool. In Baltimore, in Baltimore this year I was taking the paint off of the shoes a lot before the game just kind of playing around with it. I mean you learn new things as you go. I mean I didn't know going into it that you could take the paint off of all these shoes and make it whatever color you want. So if you look right here like that's the black check on it and then I had it change the pink. So it's kind of cool. It's a cool little touch that comes with the SB dunks. I don't know. I mean these are, this is another version of the Blazers that, these are the Serena Williams pair. Oh I saw those. I tried to get myself a pair of those. It was impossible. Yeah maybe we should set something up during the season and we'll go find you a pair. I'm sure I could get you a pair. This is one of my favorites though. These are the Nigel Sylvester ones. These are the ones that I wore really first against the Red Sox this year. This is where it kind of all started. And I think that the way that they look they look terrible. They look like they're beat up like 15 year old shoes but the shoe is designed after a biker. And it's supposed to just be like he, you know he's out riding he scuffed them up. So it's a pretty cool thing.  You want to see my favorite pair? I would like to. I want to see what you're working with. You've seen these a hundred times at the ballpark. I've seen them. I've seen them but they're good. They're good. And then these are a little bit different. I don't wear these often but I like these too. I like those. So where do you get your shoes then? Where, what does your go to? I go, a lot of it's online. I'll go to Goat Often. Sometimes I just get them straight off the Nike website. And there's another, I can't think of the website that I use. There's one other website that I go to. It might be StockX. I don't think it's StockX. I got to check that out. I got to check out. That's where I should be going. Maybe. I mean look like I don't want to influence this addiction anymore on anyone else but StockX is a really good website to find some stuff on. Well I have time. So I have time to browse the internet now so I'll check it out. Any message you'd like to give to those who are on the front lines and are putting their life on the line to try to save others? Yeah, I mean I think I'd just be more than likely echoing a lot of the same things that people have said where, you know, the gratitude that we have towards the people that are going out there and, you know, trying to make a difference in somebody's life that might be going through something is, it's something that resonates with me because I do have a friend that she's going through her final stages of her residency in San Diego and she is sick right now. I mean she hasn't gotten the results back but it seems, you know, like she could have the virus right now and it resonates more because she's in an area where she can be more sick but she's more likely to be sick. So it upsets me to see that she's going through it. It upsets me to see the other first responders, you know, do get sick and there are consequences that come with it but, you know, at the end of the day we also be very grateful for the stuff that they do to ensure that when something does happen like this that we get through it and, you know, we move on from it but, you know, I can't say thank you enough to all of them out there and, you know, just keep doing what you can do because it's all appreciated. Well, on that note, Clint, thank you so much for the time. I hope you and your family remain safe during this time. Thank you very much. You too.


Thanks Bob the Yankees are sending this one back to the Bronx tomorrow night and Jeff we spoke about it before the game Garrett Cole was going to have to set the tone in this one and he did just that this evening. He did he was outstanding is exactly what we talked about he had to go deep in the game yet eliminate some of the outs in the bullpen you only had to have six outs from the bullpen at Holmes and Peralta. The first four innings the leadoff hitter would got on from the Guardian so you're wondering how many pitches were you going to was he going to be able to go. He went 110 I was saying 115 120 he was outstanding struck out eight he had a really good knuckle curve really had a good change up as well. And those last couple innings especially the last strikeout in that seventh inning 98 miles an hour he was feeling it. That's exactly what you need from Garrett Cole and you can see the emotion as Garrett Cole walked off the mound what this meant to him. He knew his team was likely going to be able to close this one out. Now you mentioned early in the game where the Guardians made him really work early getting that leadoff runner on how was he able to overcome the adversity early on to get through seven. Yeah you know it was to me I've watched him over the years.  You know it seemed to me like just stepped off took the time slowed the game down because what do we talk about when guys struggle the game speeds up on him. He really stepped off you know luckily they didn't have the time clock but I mean he took his time and he made his pitches. He really went through a thought process. OK oh I'm in a jam. I can't let things speed up and get in trouble and make a mistake on the mound with a bad pitch. He settled down. He made the pitches when he needed to. I thought he did an outstanding job. It was his time. You know two great outings in the ALDS. That's exactly what you want. That's exactly what you needed from your.