Ancestral Circuits for the Coordinated Modulation of Brain State

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 integra...

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Bibliographic Details
Published in:Cell 2017-11, Vol.171 (6), p.1411-1423.e17
Main Authors: Lovett-Barron, Matthew, Andalman, Aaron S., Allen, William E., Vesuna, Sam, Kauvar, Isaac, Burns, Vanessa M., Deisseroth, Karl
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
Brain - cytology
Brain - physiology
Brain Mapping
Brain state
Calcium imaging
Larva - cytology
Larva - physiology
Mice
Neural Pathways
Neuromodulation
Neurons - cytology
Volume registration
Zebrafish
Zebrafish - growth & development
Zebrafish - physiology
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Summary: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. [Display omitted] •MultiMAP: registering brain-wide cellular-resolution dynamics with molecular identity•Diverse neuromodulatory cell types across the zebrafish brain correlate with alertness•Neuromodulator-specific brain-state-dependent dynamics are conserved from fish to mouse•Activation of diverse neuromodulators similarly modulates alertness-related behavior Registration of brain-wide activity measurements with multiple molecular markers at cellular resolution uncovers multiple diverse neuromodulatory pathways linked to brain state.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2017.10.021