Serotonin is a neurotransmitter thought to be involved in many behaviors. It is released by a small number of neurons throughout the brain. Little is known, however, about when and where serotonin is released, in the context of well-controlled behaviors in mammals. This proposal aims to determine functions of serotonin- and non-serotonin-releasing neurons in the dorsal raphe, the primary source of forebrain serotonin. The behaviors to be studied involve rewards and punishments, simple motivational stimuli that elicit similar behavioral responses across mammals (including humans). The goal of the project is to link action potentials from identified serotonin-releasing neurons to action potentials in nearby glutamate- or GABA-releasing neurons, and midbrain dopamine-releasing neurons, in the context of motivated behavior.
Three aims test three hypothesis that address different mechanistic questions about the functions of serotonin-releasing neurons: 1) dorsal raphe neurons signal reward and punishment rate and timing; 2) dorsal raphe signals reward probability and affective decision bias; 3) dorsal raphe is involved in generating dopaminergic reward activity. Observing activity from specific neuronal types (serotonin-, glutamate-, or GABA- releasing) in the dorsal raphe, and manipulating them while observing activity from dopamine-releasing neurons, while mice perform well-controlled behavioral tasks, will enable testing these three hypotheses. Ultimately, understanding when and where serotonin is released in the brain will be necessary in understanding affective and motivational disorders such as drug addiction and depression.

Public Health Relevance

Many disorders (for example, addiction and depression) manifest as changes in emotional behavior. Treating these disorders requires understanding how emotion is formed in the brain, but surprisingly little is known about its biological basis and the physiology of relevant circuits in the brain. The work in this proposal addresses this need using a new approach to understanding the functions of serotonin neural circuits in behavior, by observing and manipulating the activity of specific neuron types during well-controlled behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA042038-02
Application #
9351491
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Berton, Olivier Roland
Project Start
2016-09-15
Project End
2021-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205