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Transgenic Mice Lines Aid in Brain Circuit Imaging

Science Update

pyramidal neurons of the mouse cerebral cortex

A major advance in understanding the brain circuits responsible for behavior has been made possible by a number of new techniques. One involves the use of light activation of specific brain systems in behaving animals. The power of this approach, called optogenetics, is enabled by the ability to target light-sensitive proteins to specific neuron types that make up the complex circuits in the brain. To this end, neuroscientists at NIMH, NINDS, and the Howard Hughes Medical Institute have generated over 250 genetically engineered mice  lines in which the protein Cre-recombinase zeroes in on particular neurons and brain systems. Cre-recombinase is a protein that enables a host of other genetically engineered proteins, such as those used in optogenetics, to manipulate the pinpointed neurons and to study their role in behaviors including fear, anxiety, movement disorders, and addiction. As shown in this figure, Cre recombinase is targeted to pyramidal neurons in layer 5 of the cerebral cortex, the wrinkled surface of the forebrain that is involved in memory, attention, sensory awareness, thought, language, and consciousness. Different types of these neurons send projections to different brain regions. Techniques such as the one detailed here are examples of research tools that the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN ) Initiative hopes to build upon to further our understanding of the human brain.

Credit: Charles R. Gerfen, Ph.D., NIMH

Paper: Gerfen CR, Paletzki R, Heintz N. GENSAT BAC Cre-Recombinase Driver Lines to Study the Functional Organization of Cerebral Cortical and Basal Ganglia Circuits. Neuron , December 18, 2013.