The Development and Integration of Early Born SST-Expressing

在之前资助的研究中，我们发现了围产期的深层 桶状皮质内的SST-CINS而不是PV-CINS接受来自腹基底核的强烈而短暂的输入 丘脑。此外，对早期出生的深层SST-CIN的连通性的扰动 躯体感觉皮层对随后前馈抑制的建立有持久的影响 在PV Cins和深层锥体神经元之间形成回路。我们在这项建议中的目标 是双重的。首先，我们希望确定我们以前的调查结果是否反映了 通过研究丘脑、中脑和中脑之间的相互作用，建立抑制性皮质环路(目标1)。 SST和PV CIN位于大脑皮层区域内，它们在感知中起到类似的感觉作用(即 视觉)或明显不同的执行功能(如前额叶)。此外，我们将利用之前的 探索这些事件背后的生理和分子机制的发现 躯体感觉皮质。这里给出的初步调查结果表明， SST和PV CIN的成熟。在目标2中，我们将探索这样的假设，即谷氨酸- 开发中的SST CIN中的信令控制它们的连接性。具体地说，我们将检验这个假设 离子亲和性AMPA介导的信号促进SST CIN的成熟和连通性，而 MGluR1/5代谢介导的信号转导作用限制了这种连接。最后，在目标3中，我们将检查 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NuRD相关转录因子SatB1的需求，这是一种活性- 这是建立L5/6期间SST和PV CIN成熟所必需的 抑制电路。

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.