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A novel inhibitory corticostriatal circuit that expresses mu opioid receptor-mediated synaptic plasticity.

Authors
  • Munoz, Braulio1
  • Atwood, Brady K2
  • 1 Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. Electronic address: [email protected]. , (India)
  • 2 Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. , (India)
Type
Published Article
Journal
Neuropharmacology
Publication Date
Dec 01, 2023
Volume
240
Pages
109696–109696
Identifiers
DOI: 10.1016/j.neuropharm.2023.109696
PMID: 37659438
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Corticostriatal circuits are generally characterized by the release of glutamate neurotransmitter from cortical terminals within the striatum. It is well known that cortical excitatory input to the dorsal striatum regulates addictive drug-related behaviors. We previously reported that anterior insular cortex (AIC) synaptic inputs to the dorsolateral striatum (DLS) control binge alcohol drinking in mice. These AIC-DLS glutamate synapses are also the sole sites of corticostriatal mu opioid receptor-mediated excitatory long-term depression (MOR-LTD) in the DLS. Recent work demonstrates that some regions of cortex send long-range, direct inhibitory inputs into the dorsal striatum. Nothing is known about the existence and regulation of AIC-DLS inhibitory synaptic transmission. Here, using a combination of patch clamp electrophysiology and optogenetics, we characterized a novel AIC-DLS corticostriatal inhibitory circuit and its regulation by MOR-mediated inhibitory LTD (MOR-iLTD). First, we found that the activation of presynaptic MORs produces MOR-iLTD in the DLS and dorsomedial striatum. Then, we showed that medium spiny neurons within the DLS receive direct inhibitory synaptic input from the cortex, specifically from the motor cortex and AIC. Using transgenic mice that express cre-recombinase within parvalbumin-expressing inhibitory neurons, we determined that this specific cortical neuron subtype sends direct GABAergic projections to the DLS. Moreover, these AIC-DLS inhibitory synaptic input subtypes express MOR-iLTD. These data suggest a novel GABAergic corticostriatal circuit that could be involved in the regulation of drug and alcohol consumption-related behaviors. Copyright © 2023 Elsevier Ltd. All rights reserved.

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