# The role L-type calcium channels (LTCCs) in regulating dopaminergic activity during cocaine abstinence

> **NIH NIH F32** · YALE UNIVERSITY · 2021 · $39,995

## Abstract

The overall goal of this proposal is to investigate the role of endocannabinoid (ECB) signaling in
regulating distinct cortical inhibitory synapses. Physiological brain development and function are
dependent on a fine-tuned balance of synaptic excitation and inhibition. As such, dysregulation of inhibition has
been implicated in a variety of neurodevelopmental disorders. The cellular targets and consequences of
GABAergic signaling in adult animals is well understood, however the specific interneurons modulated by
ECB signaling remains poorly studied. Cortical inhibition is mediated by a diverse group of GABAergic
interneurons (INs), including cells co-expressing the calcium binding protein parvalbumin (PV), the peptide
transmitter somatostatin (SOM), or the serotonin 5HT3a receptor. Cortical INs differ in their synaptic targets,
with PV-INs making synapses onto the perisomatic and proximal dendritic regions of target pyramidal neurons
and SOM-INs making connections onto the dendritic arbors. A subset of 5HT3a-INs which express the
vasoactive intestinal peptide (VIP), innervate dendrites of pyramidal neurons and other interneurons. This
subcellular localization allows PV-INs to regulate the magnitude and timing of PN spike output and SOM-INs to
regulate dendritic spine and shaft calcium influx along with glutamatergic synaptic plasticity. While the birth and
migration of GABAergic INs is well understood, there remain gaps in our knowledge of the molecular and
cellular mechanisms that influence inhibitory signaling. ECBs influence synaptogenesis and long-term plasticity
of both excitatory and inhibitory connections. Although data has shown coexpression of the cannabinoid type-1
(CB1) receptor with SOM or VIP, colocalization of the CB1 receptor within the various interneurons has not
been studied and will be addressed in this proposal. ECB release in the cortex modulates presynaptic GABA
release and can drive both short- and long-term depression of inhibitory transmission, however the identity of
the presynaptic INs sensitive to ECB activity is not well-characterized. Moreover, the consequences of CB1
receptor loss from distinct interneurons is unknown. In this proposal, we seek to determine how ECB signaling
modulates GABAergic signaling mediated by distinct IN populations. We hypothesize that ECB signaling
modulates cortical activity, with a key role in influencing plasticity mediated by dendritic targeting
interneurons. We propose a novel combination of tools including electrophysiology, 2-photon laser-scanning
microscopy (2PLSM), and optogenetic stimulation of genetically-targeted INs in the mouse primary visual
cortex. Our experiments will provide an unprecedented level of insight into the development of GABAergic
circuits in the neocortex.

## Key facts

- **NIH application ID:** 10198057
- **Project number:** 5F32NS110111-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Nour Al-muhtasib
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,995
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198057

## Citation

> US National Institutes of Health, RePORTER application 10198057, The role L-type calcium channels (LTCCs) in regulating dopaminergic activity during cocaine abstinence (5F32NS110111-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198057. Licensed CC0.

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