细胞类型特异遗传学操作神经回路.pdfVIP

20 5 Vol. 20, No. 5 2008 10 Chinese Bulletin of Life Sciences Oct., 2008 1004-0374(2008)05-0702-05 B A C 2 0 C r e CreER GABA Cre Cre- (1) (2) (3) Cre/loxP GABA Q422; Q754 A A cell type-based genetic approach to complex neural circuits HUANG Z Josh (Cold Spring Harbor Laboratory, New York, USA) Abstract: A major challenge in modern neuroscience is to understand how behaviors emerge from the underlying neural networks and their cellular constituents. To take on this challenge, a productive approach aims to establish causal links between patterns of activity in specific groups of neurons and the computation of neural circuits that guides behavior. Using BAC recombineering (bacterial artificial chromosome engineering) technology, we are generating over 20 knockin “driver lines” expressing Cre or the inducible CreER in specific GABAergic cell types. In addition, we are constructing a new generation of Cre-activated “reporter” mice and, in particular, Cre- activated viruses to achieve high level expression of fluorescent proteins (FPs) and “molecular switches” (MSs, such as ligand- or light- induced ion channels) in vivo. These genetic strategies will allow us to: 1) visualize the morphology and connectivity of GABA interneurons with synapse resolution (genetic neuroanatomy); 2) visu- alize the activity and activity-history of interneurons (g