It is hypothesized that animals'perceptual, emotional, or behavioral processes are governed/caused by specific patterns of brain activities, or firings of selected populations (ensembles) of neurons across multiple regions in the nervous system. Indeed recent advancements in optic imaging and multi-electrode recording technology have begun to reveal the inordinately complex dynamics of large populations of neurons in awake, behaving vertebrates such as larval zebrafish and rodents. However, these visualization/recording experiments could not definitively establish the causal relationships between the activities of neuronal ensembles and their functions. A toolkit that enables neuroscientists to be not only observers, but also actuators of the observed ensembles is critically needed for "causal neuroscience". The difficulty to developing such a toolkit lies in th complexity of the mammalian brain, which contains billions of neurons and trillions of synapses. Thus, individual neurons are likely to participate in different active ensembles at different time points. Hence the ensembles associated with a given behavioral or perceptual process are emergent properties arising out of the complicated interactions among millions of neurons. Therefore, ensembles are unlikely to be genetically pre-determined, and molecule or cell-type based methods are not useful for "labeling and manipulating" them. To overcome this difficulty, we will develop a novel toolkit consisting of two key components: (1) a mouse line designed to express, transiently and selectively, a very unstable foreign receptor only in activated neurons, and (2) engineered non-toxic, pseudo-typed viruses that can only infect neurons expressing this foreign receptor. In this way, timed-injection of the pseudo-typed viruses will allow us to specifically and permanently "capture" the recently activated ensembles (which are the ones expressing the viral receptor). The engineered viruses can int

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
1DP1MH103908-01
Application #
8559171
Study Section
Special Emphasis Panel (ZRG1-BCMB-N (50))
Program Officer
Freund, Michelle
Project Start
2013-09-26
Project End
2018-07-31
Budget Start
2013-09-26
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$785,000
Indirect Cost
$285,000
Name
Duke University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Halassa, Michael M; Chen, Zhe; Wimmer, Ralf D et al. (2014) State-dependent architecture of thalamic reticular subnetworks. Cell 158:808-21