Corticothalamic control of social motivation

大脑皮质丘脑对社会动机的控制 摘要 社交障碍是抑郁症、精神分裂症等精神障碍的常见症状， 和自闭症。然而，大脑处理社会信息并使用它来引导 社交行为仍不明朗。在人类和啮齿动物中，内侧前额叶皮质(MPFC)被认为 自上而下对社会行为的抑制控制，但涉及的不同神经回路尚未阐明。 虽然mPFC神经元的非特异性全局激活降低了社交能力，但最近的报告表明，这些影响 是由丘脑中线核丘脑室旁后核(PPVT)的活动变化调节的 已知在动机和情绪化行为中起作用。这项建议旨在确定小白蛋白 (PV)在pPVT投射的mPFC神经元中，mPFC门活动中的中间神经元调节社会动机。我们的 初步数据表明，mPFC-pPVT通路的化学激活抑制了男性的社会动机 但不是雌性老鼠。根据这一观察结果，我们假设pPVT投射的mPFC神经元施加顶端... 以特定性别的方式向下抑制对社会动机的控制。在雄性小鼠身上，我们预测有效 社会参与需要通过激活附近的PV来抑制mPFC-pPVT电路的活动 中间神经元。这一假设将使用转基因小鼠、病毒光遗传构建物、 行为测试、活体钙成像和膜片钳记录。目标一号将利用光遗传学精确地 激活或抑制pPVT中mPFC神经元的轴突终末，以揭示操纵这一电路是如何调节的 社会动机。AIM 2将通过纤维光度学、化学遗传学、 和转基因小鼠，以确定mPFC-pPVT神经元在社会互动过程中是否沉默 这种方式依赖于PV中间神经元的活动。目标3将确定生理差异是否存在于 雄性和雌性小鼠之间的mPFC-pPVT回路。这项研究将提供第一个针对性别的证据 MPFC-pPVT通路是以前被忽视的社交脑的一个组成部分，特别是在女性 以及对mPFC中PV中间神经元在大脑中起作用的电路机制的新见解 对社会动机的调节。

Corticothalamic control of social motivation Abstract Social impairments are a common symptom among psychiatric disorders such as depression, schizophrenia, and autism. However, the mechanisms by which the brain processes social information and uses it to guide social behaviors remain unclear. In humans and rodents, the medial prefrontal cortex (mPFC) is thought to exert top-down inhibitory control over social behaviors, but the distinct neural circuitry involved has yet to be elucidated. While non-specific global activation of mPFC neurons decreases sociability, recent reports indicate these effects are mediated by activity changes in the posterior paraventricular thalamus (pPVT), a midline thalamic nucleus known to play a role in motivated and emotional behaviors. This proposal aims to determine whether parvalbumin (PV) interneurons in the mPFC gate activity in pPVT-projecting mPFC neurons to regulate social motivation. Our pilot data indicate that chemogenetic activation of mPFC-pPVT pathway suppressed social motivation in male but not female mice. Based on this observation, we hypothesize that pPVT-projecting mPFC neurons exert top- down inhibitory control over social motivation in a sex-specific manner. In male mice, we predict that effective social engagement requires suppressed activity of the mPFC-pPVT circuit mediated by activation of nearby PV interneurons. This hypothesis will be tested using a combination of transgenic mice, viral optogenetic constructs, behavioral testing, in vivo calcium imaging, and patch-clamp recording. Aim 1 will use optogenetics to precisely activate or inhibit axonal terminals of mPFC neurons in the pPVT to reveal how manipulating this circuit regulates social motivation. Aim 2 will combine pathway-specific calcium imaging via fiber photometry, chemogenetics, and transgenic mice to determine whether mPFC-pPVT neurons are silenced during social interaction in a manner that is dependent on PV interneuron activity. Aim 3 will determine if physiological differences exist in the mPFC-pPVT circuit between male and female mice. This study will provide the first sex-specific evidence that the mPFC-pPVT pathway represents a previously overlooked component of the social brain, especially in female mice, and novel insights into the circuit mechanisms by which the PV interneurons in the mPFC play in the regulation of social motivation.