Tomato fluorescence in the mouse brainstem

Our research focuses on the functional neuroanatomy of the mammalian hypothalamus. We work mainly on the regulation of body weight homeostasis, food intake, and control of the autonomic nervous system. Our current projects involve investigating the central mechanisms underlying the actions of leptin, melanocortins, orexin, glucagon-like peptide 1, and serotonin.

The work going on in our laboratory focuses on identifying the pathways in the brain involved in regulating autonomic functions, such as body weight regulation, thermoregulation, and cardiovascular control. Homeostasis is maintained by motivated behaviors subserving these basic vital functions. The hypothalamus is critical for regulating each of these processes and behaviors, but the complex hypothalamic circuits that underlie these responses have remained difficult to characterize. Whereas, unraveling these interactions once seemed a far-off goal, progress in the last few years in determining critical genes that regulate body weight has given us tools to dissect the neuronal pathways, neurotransmitters, and physiological responses that result in homeostasis.

The availability of these new molecular tools, coupled with more traditional neuroanatomic techniques including tract tracing and whole animal physiology, has allowed the identification of an extensive network of hypothalamic circuitry that may regulate feeding, insulin secretion, cardiovascular control, and body weight homeostasis.

We are using conditional, neuron-specific gene-targeting methods to determine the functional importance of these neurocircuits in controlling body weight. Techniques being utilized include BAC transgenesis, neuron-specific knockouts, neuron-specific gene reactivations, and neuron-specific cell ablation.

Double-labeling hypothalamic leptin-sensitive neurons
Double-labeling of sensory ganglion
Parasympathetic neurons
Neuropeptidergic neurons in the hypothalamus