The Development and Integration of Early Born SST-Expressing

早期出生 SST 表达的发展和整合

• 批准号: 10176605
• 负责人: GORDON J FISHELL
• 金额: $ 53.57万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176605
• 关键词: Affective; Area; Award; Behavioral; Brain Diseases; Cells; Cerebral cortex; Development; Disease; Epigenetic Process; Epilepsy; Etiology; Event; Excision; Funding; Genetic; Goals; Grant; Hindlimb; Interneurons; Knockout Mice; Laboratories; Mediating; Metabotropic Glutamate Receptors; Minority; Molecular; Morphology; Mutation; Nature; Paper; Parvalbumins; Perception; Perinatal; Physiological; Population; Publishing; Reflex action; Role; Schizophrenia; Seizures; Sensory; Signal Transduction; Sleep; Somatosensory Cortex; Somatostatin; Structure; Testing; Thalamic structure; Visual; Work; area striata; barrel cortex; critical period; executive function; experimental study; glutamatergic signaling; hippocampal pyramidal neuron; nervous system disorder; progenitor; risk variant; somatosensory; transcription factor

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.

在之前的资助期内支持的研究中，我们发现围产期深层