Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice.
Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice.
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DOI：
10.1038/s41386-021-01050-1
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Crowley NA
中科院分区：
文献类型：
--
作者：
Dao NC;Brockway DF;Suresh Nair M;Sicher AR;Crowley NA
生长抑素（SST）神经元与多种神经精神疾病（如抑郁和焦虑）有关，但它们在物质使用障碍（包括酒精使用障碍（AUD））中的作用尚未完全确定。在这里，我们发现通过在黑暗中饮酒（DID）模型的反复饮酒循环导致前边缘（PL）皮层SST神经元的活动减少，减少了它们的动作电位放电能力和兴奋/抑制传递动态。我们研究了它们在通过双向化学遗传学操作调节酒精消费中的作用。hm3dq诱导的PL SST神经元兴奋和kord诱导的沉默都减少了雄性和雌性的酗酒，但对糖的消耗没有影响。酗酒通过增加SST神经元介导的GABA释放和其他GABA能群体的突触强度，减少自发抑制传递到锥体神经元来解除锥体神经元的抑制。锥体神经元还表现出增强的内在兴奋性。通过hM4Di直接抑制PL锥体神经元足以减少酗酒。综上所述，这些数据揭示了前皮层中一个由sst介导的微电路调节锥体神经元的抑制动力学，锥体神经元是皮层下目标的主要输出源，驱动寻求奖励行为和情绪反应。
Somatostatin (SST) neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance use disorders, including alcohol use disorder (AUD), is not fully characterized. Here, we found that repeated cycles of alcohol binge drinking via the Drinking-in-the-Dark (DID) model led to hypoactivity of SST neurons in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. Alcohol binge drinking disinhibited pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations and reducing spontaneous inhibitory transmission onto pyramidal neurons. Pyramidal neurons additionally displayed increased intrinsic excitability. Direct inhibition of PL pyramidal neurons via hM4Di was sufficient to reduce alcohol binge drinking. Together these data revealed an SST-mediated microcircuit in the PL that modulates the inhibitory dynamics of pyramidal neurons, a major source of output to subcortical targets to drive reward-seeking behaviors and emotional response.
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