Journal
CELL
Volume 171, Issue 6, Pages 1411-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2017.10.021
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Funding
- Howard Hughes Medical Institute (HHMI) fellowship from the Helen Hay Whitney Foundation (HHWF)
- Brain and Behavior Research Foundation (BBRF)
- HHWF
- BBRF
- Fannie and John Hertz Foundation Fellowship
- NSF Graduate Research Fellowship
- NIMH [R01MH099647]
- NIDA [P50DA042012]
- DARPA (NeuroFAST program) [W911NF-14-2-0013]
- NOMIS Foundation
- Else Kroner Fresenius Foundation
- Wiegers Family Fund
- James Grosfeld Foundation
- Sam and Betsy Reeves Foundation
- HL Snyder Foundation
- Tarlton Foundation
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Internal states of the brain profoundly influence behavior. Fluctuating states such as alertness can be governed by neuromodulation, but the underlying mechanisms and cell types involved are not fully understood. We developed a method to globally screen for cell types involved in behavior by integrating brain-wide activity imaging with high-content molecular phenotyping and volume registration at cellular resolution. We used this method (MultiMAP) to record from 22 neuromodulatory cell types in behaving zebrafish during a reaction-time task that reports alertness. We identified multiple monoaminergic, cholinergic, and peptidergic cell types linked to alertness and found that activity in these cell types was mutually correlated during heightened alertness. We next recorded from and controlled homologous neuromodulatory cells in mice; alertness-related cell-type dynamics exhibited striking evolutionary conservation and modulated behavior similarly. These experiments establish a method for unbiased discovery of cellular elements underlying behavior and reveal an evolutionarily conserved set of diverse neuromodulatory systems that collectively govern internal state.
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