The many classes of neurons in the mammalian brain use many different neurotransmitters to communicate. Nevertheless, it has generally been assumed that each neuron uses one principal neurotransmitter. This notion has dominated the analysis of the contributions of synaptic transmission to circuit function and behavior. However, we and others have found that many neurons in the mammalian brain actually release several neurotransmitters at the same time, often targeting each neurotransmitter to a specific and different postsynaptic cell class. We propose that the co-released neurotransmitters act in concert to have consistent and mutually reinforcing effects on their enclosing circuit. Here we propose to study the integration and coordination of peptidergic, GABAergic, and cholinergic signaling and reveal how these diverse signaling molecules act together to dictate the activity and plasticity state of cerebral cortex. The pathways that we have uncovered are potentially powerful means of regulating cortical function and may, in the future, be exploited to restore cognitive function in neurodegenerative disorders.

Public Health Relevance

Neurons in the brain communicate using a large diversity of chemical signals and it is the concerted action of these signals that determine the activity and plasticity of neural circuits as well as animal behavior. We propose to follow up on previous findings from the lab that reveal that many individual neurons actually release multiple chemicals, each onto different classes of cells. We will determine how the integrated and simultaneous action of these molecules controls brain circuitry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS046579-17
Application #
10057394
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Churn, Severn Borden
Project Start
2004-02-01
Project End
2021-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
17
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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