Department of Neurobiology; The Brudnick Neuropsychiatric Research Institute; Graduate School of Biomedical Sciences; Martin Lab; Tapper Lab
Molecular and Cellular Neuroscience | Substance Abuse and Addiction
The nucleus accumbens (NAc) is a forebrain region mediating the positive-reinforcing properties of drugs of abuse, including alcohol. It receives glutamatergic projections from multiple forebrain and limbic regions such as the prefrontal cortex (PFCx) and basolateral amygdala (BLA), respectively. However, it is unknown how NAc medium spiny neurons (MSNs) integrate PFCx and BLA inputs, and how this integration is affected by alcohol exposure. Because progress has been hampered by the inability to independently stimulate different pathways, we implemented a dual wavelength optogenetic approach to selectively and independently stimulate PFCx and BLA NAc inputs within the same brain slice. This approach functionally demonstrates that PFCx and BLA inputs synapse onto the same MSNs where they reciprocally inhibit each other pre-synaptically in a strict time-dependent manner. In alcohol-naive mice, this temporal gating of BLA-inputs by PFCx afferents is stronger than the reverse, revealing that MSNs prioritize high-order executive processes information from the PFCx. Importantly, binge alcohol drinking alters this reciprocal inhibition by unilaterally strengthening BLA inhibition of PFCx inputs. In line with this observation, we demonstrate that in vivo optogenetic stimulation of the BLA, but not PFCx, blocks binge alcohol drinking escalation in mice. Overall, our results identify NAc MSNs as a key integrator of executive and emotional information and show that this integration is dysregulated during binge alcohol drinking.
basolateral amygdala, binge alcohol drinking, decision making, nucleus accumbens, optogenetics, prefrontal cortex, synaptic integration
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Copyright © 2021 Kolpakova, van der Vinne, Giménez-Gómez, Le, You, Zhao-Shea, Velazquez-Marrero, Tapper and Martin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI of Published Version
Kolpakova J, van der Vinne V, Giménez-Gómez P, Le T, You IJ, Zhao-Shea R, Velazquez-Marrero C, Tapper AR, Martin GE. Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons. Front Cell Neurosci. 2021 Nov 16;15:742207. doi: 10.3389/fncel.2021.742207. PMID: 34867199; PMCID: PMC8635139. Link to article on publisher's site
Frontiers in cellular neuroscience
Kolpakova J, van der Vinne V, Gimenez-Gomez P, Le T, You I, Zhao-Shea R, Velazquez-Marrero C, Tapper AR, Martin GE. (2021). Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons. UMass Chan Medical School Faculty Publications. https://doi.org/10.3389/fncel.2021.742207. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2195
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