Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons.
Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons.
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DOI：
10.3389/fncel.2021.742207
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发表时间：
2021
影响因子：
5.3
通讯作者：
Martin GE
中科院分区：
文献类型：
--
作者：
Kolpakova J;van der Vinne V;Giménez-Gómez P;Le T;You IJ;Zhao-Shea R;Velazquez-Marrero C;Tapper AR;Martin GE
伏隔核（NAc）是一个前脑区域，介导药物滥用（包括酒精）的积极强化特性。它分别接受来自前额皮质（PFCx）和杏仁核基底外侧（BLA）等多个前脑和边缘区域的谷氨酸能投射。然而，NAc介质棘神经元（msn）如何整合PFCx和BLA输入，以及这种整合如何受到酒精暴露的影响，目前尚不清楚。由于无法独立刺激不同通路阻碍了进展，我们实施了双波长光遗传方法来选择性地独立刺激同一脑切片内的PFCx和BLA NAc输入。这种方法在功能上证明了PFCx和BLA输入在相同的msn上突触，它们在突触前以严格的时间依赖方式相互抑制。在alcohol-naïve小鼠中，PFCx事件对bla输入的时间门控比相反的门控更强，这表明msn优先考虑来自PFCx的高阶执行过程信息。重要的是，酗酒通过单方面加强BLA对PFCx输入的抑制，改变了这种相互抑制。根据这一观察结果，我们证明了BLA的体内光遗传刺激，而不是PFCx，可以阻止小鼠酗酒的升级。总的来说，我们的研究结果确定NAc msn是执行和情绪信息的关键整合者，并表明这种整合在酗酒期间失调。
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-naïve 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.
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影响因子：
7.6
作者：
Millan, E. Zayra;Reese, Rebecca M.;Janak, Patricia H.
通讯作者：
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