室旁丘脑通过多突触抑制边缘 CRF 神经元，从而依赖性地减少小鼠的 binge 饮酒和回避行为。
The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice.
机构信息
Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA.
出版信息
Nat Commun. 2021 Aug 23;12(1):5080. doi: 10.1038/s41467-021-25368-y.
Bed nucleus of the stria terminalis (BNST) neurons that synthesize corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety. Here, we found that female C57BL/6J mice binge drink more than males and have greater basal BNST neuron excitability and synaptic excitation. We identified a dense VGLUT2 + synaptic input from the paraventricular thalamus (PVT) that releases glutamate directly onto BNST neurons but also engages a large BNST interneuron population to ultimately inhibit BNST neurons, and this polysynaptic PVT-BNST circuit is more robust in females than males. Chemogenetic inhibition of the PVT projection promoted binge alcohol drinking only in female mice, while activation reduced avoidance behavior in both sexes. Lastly, repeated binge drinking produced a female-like phenotype in the male PVT-BNST excitatory synapse without altering the function of PVT neurons per se. Our data describe a complex, feedforward inhibitory PVT-BNST circuit that is sex-dependent in its function, behavioral roles, and alcohol-induced plasticity.
终纹床核（BNST）中的促肾上腺皮质释放因子（CRF）合成神经元会驱动 binge drinking 和焦虑。在这里，我们发现雌性 C57BL/6J 小鼠比雄性小鼠更易 binge drinking，并且基础 BNST 神经元兴奋性和突触兴奋性更高。我们发现来自室旁核（PVT）的密集 VGLUT2+突触输入，它直接将谷氨酸释放到 BNST 神经元上，也会激活大量 BNST 中间神经元，最终抑制 BNST 神经元，而这个多突触 PVT-BNST 回路在雌性中比雄性更强大。化学遗传抑制 PVT 投射仅在雌性小鼠中促进 binge drinking，而激活则减少了两性的回避行为。最后，重复 binge drinking 在不改变 PVT 神经元功能本身的情况下，在雄性 PVT-BNST 兴奋性突触中产生了类似雌性的表型。我们的数据描述了一个复杂的、前馈抑制性 PVT-BNST 回路，其功能、行为作用和酒精诱导的可塑性在性别上存在差异。
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