权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neural Mechanism for the assembly of GABAergic in the cerebral cortex

大脑皮层中 GABA 能组装的神经机制

基本信息

批准号：
10594516
负责人：
Natalia Vanesa De Marco Garcia
金额：
$ 42.38万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10594516
关键词：
ASD patient Adolescent Adult Affect Area Behavior Behavioral Brain Brain Diseases Calcium Cells Cerebral cortex Cortical Column Defect Development Developmental Process Disease Distal Emergency Situation Epilepsy Equilibrium Etiology Functional disorder Goals Human Image Impairment Interneuron function Interneurons Knowledge Lasers Lateral Lead Ligands Microscopy Mus Mutant Strains Mice Neonatal Neurons Outcome Output Perinatal Photons Population Process Research Rest Role Scanning Schizophrenia Sensory Sensory Deprivation Shapes Somatosensory Cortex Study models System Techniques Testing Thalamic structure Vibrissae Work autism spectrum disorder barrel cortex brain abnormalities chemokine childhood epilepsy critical period excitatory neuron gamma-Aminobutyric Acid genetic approach hippocampal pyramidal neuron in vivo in vivo calcium imaging inhibitory neuron innovation insight maladaptive behavior neonate nervous system disorder neurological pathology neuromechanism neurotrophic factor perinatal development postnatal postnatal development pup recruit sensor sensory integration somatosensory translational impact two-photon

项目摘要

Project Summary Dysfunction of gamma-aminobutyric acid (GABA)ergic interneurons is strongly associated with neurological disorders including epilepsy, schizophrenia and autism spectrum disorders. Although recent evidence highlights bewildering subtype diversity of these neurons, the notion that developmental perturbations in subtype function cause defects in the formation of cortical circuits with lasting functional deficits has not been explored in detail. The long-term goal of this research is to uncover how early interneuron dysfunction in the developing postnatal brain leads to lasting neurological pathologies. The objective of this proposal is to reveal how the activity of specific interneuron populations during critical windows of perinatal development shape circuits underlying primary sensory-dependent behavior. To this end, we will use the murine barrel cortex as a well-established model for the study of activity-dependent circuit maturation. We will focus our studies in superficial circuits since our previous work indicates that these circuits are exquisitely sensitive to environmental perturbations in the neonate. In the near term, this proposal is aimed at investigating the role of layer I interneuron subtypes in regulating the emergence of cortical columns (Aim 1). In addition, this project will determine the role of LI interneurons in the emergence of interhemispheric circuits. (Aim 2). Finally, we will assess how developmental defects in early LI interneuron function lead to abnormal brain activity and impaired sensory integration in the adult (Aim 3). With respect to the outcomes, our work is expected to identify basic mechanisms fundamental for the emergency of a healthy excitatory/inhibitory balance. In addition, these results are expected to have a significant translational impact because they will expand our mechanistic knowledge on how early interneuron dysfunction may lead to behavioral abnormalities frequently observed in ASD patients.

项目总结