Inhibitory neuron circuit organization and function in prefrontal cortex.

前额皮质的抑制性神经元回路组织和功能。

基本信息

批准号：
9178673
负责人：
Peyman Golshani
金额：
$ 2.85万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
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：
2016-03-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9178673
关键词：
Action Potentials Animals Area Attention Deficit Disorder Autistic Disorder Behavior Behavior Control Behavioral Brain Brain Diseases Cells Cognition Complement Control Animal Data Disease Distant Electrophysiology (science)Feedback Functional disorder Future Generations Genetic Head Injury Interneurons Laboratories Lasers Learning Link Maps Measures Medial Motivation Mus Neurons Output Parvalbumins Pattern Performance Physiological Prefrontal Cortex Preparation Rabies Regulation Research Rewards Role Scanning Schizophrenia Shapes Slice Somatostatin Synapses System Testing Time Training Vasoactive Intestinal Peptide Water adaptive learning auditory stimulus awake base cell type chemical group cognitive control connectome excitatory neuron executive function in vivo information processing inhibitory neuron nervous system disorder neural circuit neuronal circuitry neuropsychiatric disorder neurotransmission new technology operation photoactivation public health relevance research study sensory cortex therapeutic target visual stimulus

项目摘要

DESCRIPTION (provided by applicant): Inhibitory neurons are key regulators of cortical operations. Their dysfunction has been implicated as a major factor in many brain disorders. While recent studies indicate physiological and functional differences between specific types of inhibitory neurons, neural circuit mechanisms that give rise to these differences in cortical regions underlying cognition and executive function are not well understood. We focus our studies of inhibitory neuron circuit organization and function in the prelimbic area of medial prefrontal cortex (mPFC). This region is highly relevant to schizophrenia, autism, attention deficit disorders and others. The guiding hypothesis for this proposal is that the distinct connectivity of each type of inhibitory neurons differentially governs computationally distinct neural signal transformations in the mPFC, and that circuit connectivity differences between these cell types can be mapped to determine their specific roles in regulation of cortical network dynamics and behavioral output. Our proposed experiments will focus on the three major, non- overlapping inhibitory cell types or groups (parvalbumin-expressing, somatostatin-expressing and vasoactive intestinal peptide-expressing interneurons). A new Cre-dependent, genetically modified rabies-based tracing system will be used to map monosynaptic global circuit connections in the intact brain to these selected inhibitory neurons. To complement the anatomical rabies tracing, physiological input characterization will be accomplished by laser scanning photostimulation and channelrhodopsin (ChR2)-assisted circuit mapping. These studies will allow mapping of both local and long-range functional inputs to identified subtypes within each targeted cell group in brain slice preparations. Building on assessing input connections, we will map local functional outputs of these major inhibitory neuronal groups. Computational and behavioral analysis of the input and output circuit connections of specific inhibitory neuron types will be applied to understand how they regulate mPFC network oscillations in vivo and how they contribute to mPFC-controlled animal learning. This will be achieved by electrophysiological recordings made in parallel with behavioral performance measures with cell-type specific genetic inactivation. Together, the proposed research will generate new maps of inhibitory neuronal circuit wiring in medial prefrontal cortex, and it will broadly illuminate how inhibitory neuronal circuits regulate normal and maladaptive behaviors linked to neuropsychiatric and neurological diseases.

描述（适用提供）：抑制神经元是皮质操作的关键调节剂。它们的功能障碍已被实施，是许多脑部疾病的主要因素。虽然最近的研究表明特定类型的抑制性神经元之间的身体和功能差异，但在认知和执行功能下的皮质区域中引起这些差异的神经记录机制尚不清楚。我们将研究集中在内侧前额叶皮层（MPFC）的抑制性神经元电路组织和功能中。该地区与精神分裂症，自闭症，注意力缺陷障碍和其他地区高度相关。该提案的指导假设是，每种类型的抑制性神经元的独特连通性差异地控制了MPFC中计算上不同的神经元信号转换，并且可以映射这些细胞类型之间的电路连接差异以确定它们在调节皮质网络动态和行为输出调节中的特定作用。我们提出的实验将集中于三种主要的非重叠抑制细胞类型或组（表达白蛋白的表达，表达生长抑素和血管活性肠肽表达神经元）。一个新的基于CRE的，基于转基因的狂犬病的追踪系统将用于将完整大脑中的单突触全局电路连接映射到这些选择的抑制性神经元中。为了完成解剖学狂犬病的追踪，将通过激光扫描光刺激和通道旋转（CHR2）辅助电路映射来实现物理输入表征。这些研究将允许将局部和远程功能输入映射到脑切片制剂中每个靶向细胞组中识别的亚型。在评估输入连接的基础上，我们将绘制这些主要抑制性神经元组的局部功能输出。将应用特定抑制性神经元类型的输入和输出电路连接的计算和行为分析，以了解它们如何调节体内MPFC网络振荡，以及它们如何促进MPFC控制的动物学习。这将通过与细胞类型特异性遗传失活的行为性能度量并行作出的电生理记录来实现。拟议的研究将共同产生培养基前额叶皮层中抑制性神经元电路接线的新图，它将广泛阐明抑制性神经元电路如何调节与神经精神病学和神经系统疾病有关的正常和不良适应行为。