Neural circuits encode animal behaviors, and neuroplasticity induces long-lasting changes in neural circuits and animal behaviors. Neural circuits are formed by billions of neurons, which communicate mostly through synapses. Neuroplasticity occurs at the synapse, as neuronal activity modulates synaptic strength through a process known as synaptic plasticity. However, there is no tool to modulate synaptic transmission mimicking synaptic plasticity in vivo. The lack of such a tool makes it difficult to study long-lasting plastic changes in animal behaviors. Here we aim to develop and validate novel molecular tools to modulate excitatory synaptic transmission in the brain. The development and validation of this innovative tool will allow us to modulate neuronal circuits and brain activity so as to elucidate the process of synaptic plasticity and to identify the mechanisms underlying animal behavior. Because hyper- or hypo-activation of synapses causes synaptopathy and because the synapse is modulated by neuronal activity, we may utilize this tool to identify precise circuits/mechanisms that underpin higher-order brain functions including learning and memory, with potential applications to the treatment of neurological disorders. Furthermore, success in this approach may allow us to manipulate distinct properties of synaptic activity including inhibitory or calcium permeability in order to investigate synaptic function in detail. Therefore, the establishment of novel tools to manipulate synaptic activity will impact and stimulate a broad area of research pertaining to brain function.

Public Health Relevance

Neural circuits encode animal behaviors and long-sustained changes in synaptic transmission induce long-lasting changes in neural circuits and animal behaviors. Unregulated alterations in neural circuits and synaptic transmissions cause neurological or mental disorders in humans. Thus, it is critical for human health to reveal how altered synaptic transmission causes diseases by developing novel tool to modulate synaptic transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Multi-Year Funded Research Project Grant (RF1)
Project #
1RF1MH114078-01
Application #
9379926
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Freund, Michelle
Project Start
2017-08-01
Project End
2020-07-31
Budget Start
2017-08-01
Budget End
2020-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520