Presynaptic modulation of synaptic inhibition onto hippocampal pyramidal neurons
Ended Project Grant Awarded Last action
- Award ID
- R56NS129556
- Recipient
-
The Research Foundation For The State University Of New York UEI NHH3T1Z96H29 Part of The Research Foundation For The State University Of New York
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $460,974
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date
- Originally
- Place of performance
- New York, USA
Award details come from USAspending.gov.
Description
- Abstract
- Throughout the hippocampus, pyramidal cells integrate excitatory and inhibitory inputs from a diverse population of interneurons. These cells provide feedforward and feedback inhibition onto CA1 pyramidal cells, and can be recruited via glutamate spillover, a phenomenon that describes non-synaptic actions of glutamate diffusing away from the synaptic cleft. The current prevailing view is that glutamate spillover leads to activation of presynaptic group III metabotropic (mgluriii) glutamate receptors, which inhibit synaptic excitation and inhibition only onto interneurons, not CA1 pyramidal cells. Against this interpretation, our preliminary data indicates that spillover activation of mgluriii receptors also exists at inhibitory synapses formed onto CA1 pyramidal cells. The main goals in this application are: (i) to determine how mgluriii activation via glutamate spillover varies between excitatory and inhibitory inputs, and among inhibitory inputs formed by different classes of interneurons; (II) to identify the intracellular signaling mechanisms that couple mgluriii activation to neurotransmitter release; (III) the determine the sub-cellular location of different type of mgluriii receptors at different types of inhibitory synapses onto CA1 pyramidal cells; (IV) to determine how spillover activation of mgluriii alters encoding of spatial information by hippocampal CA1 place cells in vivo. The proposed experiments capitalize on in vitro and in vivo electrophysiology, and EM approaches. These findings will generate new information on the operating principles of neuronal circuits involved in spatial map representation and will contribute to the future development of effective strategies to treat disease states associated with hippocampal neural circuit dysfunction, like epilepsy and autism spectrum disorder.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$130 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $461,104 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Universita' Politecnica Delle Marche | $57,509 | |
| Brandeis University | $135,226 |
Quick answers
Who received award R56NS129556?
R56NS129556 was awarded to The Research Foundation For The State University Of New York by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on September 1, 2023.
How much is award R56NS129556 worth?
$460,974 has been obligated on R56NS129556.
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