The Development and Integration of Early Born SST-Expressing

在上一个资助期支持的研究中，我们发现围产期深层 桶状皮质内的SST-cIN而不是PV-cIN接受来自腹基底核的强烈但短暂的输入 丘脑此外，扰动的连接早期出生的深层SST-cIN内的 躯体感觉皮层对随后前馈抑制的建立有持久的影响 PV cINs和深层锥体神经元之间形成回路。我们在本提案中的目标 是双重的。首先，我们希望确定我们以前的发现是否反映了一个普遍的原则， 通过检查丘脑， 皮层区域内的SST和PV cIN在感知中起类似的感觉作用（即， 视觉）或明显不同的执行功能（即前额）。此外，我们将利用我们以前的 研究结果，探索这些事件背后的生理和分子机制， 躯体感觉皮层这里提出的初步调查结果表明， SST和PV cIN的成熟。在目标2中，我们将探讨谷氨酸模式的假设- 发育中的SST cIN内的信号传导控制它们的连接。具体来说，我们将测试假设 离子型AMPA介导的信号传导促进SST cINs的成熟和连接， mGluR 1/5促代谢介导的信号传导起到限制这种连接性的作用。最后，在目标3中，我们将研究 在这些事件发生期间，SST和PV cIN内发生的分子变化。我们 还将探索对与HD-A相关的转录因子SatB 1的需求，SatB 1是活性- 依赖于L5/6的建立，并且是SST和PV cIN成熟所必需的 抑制回路

In the studies supported during the previous funding period we discovered that perinatally deep layer SST-cINs but not PV-cINs within the barrel cortex receive strong but transient input from the ventrobasal thalamus. In addition, perturbations to the connectivity of early born deep layer SST-cIN within the somatosensory cortex have a lasting impact on the subsequent establishment of the feedforward inhibitory circuits formed between PV cINs and deep layer pyramidal neurons. Our goals within the present proposal are two-fold. First, we wish to determine whether our previous findings reflect a general principle underlying the establishment of inhibitory cortical circuitry (Aim 1) by examining the interactions between thalamus, SST and PV cINs within regions of the cortex that either subserve a similar sensory role in perception (i.e. visual) or markedly different executive functions (i.e. prefrontal). Moreover, we will leverage our previous findings to explore the physiological and molecular mechanisms underlying these events in the somatosensory cortex. Preliminary findings presented here demonstrate a requirement for activity for the maturation of both SST and PV cINs. In Aim 2, we will explore the hypothesis that the mode of glutamate- signaling within developing SST cINs controls their connectivity. Specifically, we will test the hypothesis that ionotropic AMPA-mediated signaling promotes maturation and connectivity of SST cINs, while mGluR1/5 metabotropic-mediated signaling acts to limit this connectivity. Finally, in Aim 3, we will examine the molecular changes that occur within SST and PV cINs during the periods when these events occur. We will also explore the requirement for the NURD-associated transcription factor SatB1, which is activity- dependent and is required for the maturation of SST and PV cINs both in the establishment of L5/6 inhibitory circuitry.