Actin cytoskeleton in postsynaptic structure and function

Active Project Grant Awarded Last action

Award ID
R01MH133798
Recipient
Awarding agency
Obligated
$2,839,480

Award facts

Assistance listing
93.242 Mental Health Research Grants
Completion date 67% complete
Place of performance
Atlanta, GA 30322, USA

Award details come from USAspending.gov.

Description

Abstract
Chemical synapses are composed of paired pre- and post-synaptic terminals. Most of the excitatory synapses reside on dendritic spines, a type of dendritic protrusion that hosts neurotransmitter receptors and other postsynaptic specializations. Synapses are plastic and undergo short- and long-term modifications during developmental refinement of neuronal circuitry, as well as during learning and memory. Synaptic modifications involve both pre- and post-synaptic changes. At the postsynaptic site, directed trafficking of neurotransmitter receptors to and from the membrane surface is believed to be a key event underlying long- term potentiation (LTP) and depression (LTD), respectively. In addition, dendritic spines undergo rapid changes in their morphology during plasticity. The underlying cellular mechanisms that control and regulate these rapid changes in postsynaptic receptors and spine structures remain to be fully elucidated. The cytoskeleton controls many, if not all, aspects of the motility of cellular structures. How the cytoskeleton regulates postsynaptic structure, function, and modifications during plasticity, however, remains poorly understood. This proposed study aims to investigate novel actin mechanisms that enable the development of postsynaptic structure and specialization required for a functional synapse. Specifically, we will investigate how actin crosslinking, (+) capping, and dynamic g-actin regulation work in concert to enable the elaboration and maturation of dendritic spines as well as to regulate their remodeling during synaptic plasticity. Furthermore, the study will a novel interaction between (+) end capping protein CP and shank scaffolding protein in coupling the actin-based structural changes and the development of the postsynaptic specialization. Given that many neural disorders are associated with alterations in synaptic connections and plasticity, we hope to gain a better understanding of the molecular and cellular mechanisms underlying synaptic plasticity, which is of importance to our understanding of brain development and functions under both physiological and pathological conditions.

Transactions

Action Obligated Date
Amendment $548,622
Amendment $83,548
Amendment $83,548
Amendment $473,444
Amendment $473,444
Amendment $588,437
Original award $588,437

Subawards

Subrecipient Amount Awarded
The Washington University Actin cytoskeleton in postsynaptic structure and function $58,583
The Washington University $48,800
The Washington University $56,302

Quick answers

Who received award R01MH133798?

R01MH133798 was awarded to Emory University by National Institute of Mental Health (National Institutes of Health) on June 3, 2024.

How much is award R01MH133798 worth?

$2,839,480 has been obligated on R01MH133798.

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