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Connectivity and function of inhibitory neurons in the primate visual cortex

灵长类视觉皮层抑制性神经元的连接和功能

基本信息

批准号：
10434932
负责人：
Alessandra Angelucci
金额：
$ 44.24万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10434932
关键词：
Address Anatomy Animal Model Anxiety Area Autopsy Axon Behavioral Biological Models Brain Calcium Callithrix Cell Nucleus Cells Cerebral cortex Chemicals Computer Models Contrast Sensitivity D Cells Data Defect Dendrites Development Disease Electrodes Electrophysiology (science)Enterobacteria phage P1 Cre recombinase Epilepsy Equilibrium Explosion Feedback Foundations Functional disorder Gene Expression Geometry Glutamates Goals Human Image Immunohistochemistry Knowledge Lateral Literature Location Maps Measures Mediating Mental disorders Morphology Mus Myoepithelial cell Neocortex Neurologic Neurons Opsin Parvalbumins Pattern Physiological Population Primates Property Publishing Rabies virus Recurrence Rodent Role Schizophrenia Sensory Somatostatin Source Stimulus Stress Stroke Technology Testing Transgenes V1 neuron Vasoactive Intestinal Peptide Viral Vision Visual Visual Cortex Work area striata autism spectrum disorder base brain dysfunction calcium indicator cell type genetic manipulation in vivo inhibitory neuron insight molecular marker nervous system disorder neural circuit neuronal cell body optogenetics receptive field response selective expression sensory cortex tool two-photon visual processing visual stimulus

项目摘要

PROJECT SUMMARY In the mammalian neocortex, inhibitory neurons (INs) profoundly influence cortical computations and dynamics, and their various functions are thought to be mediated by different IN types. While a large diversity of INs exists, molecular markers in mouse cortex identify three major non-overlapping classes: parvalbumin- (PV), somatostatin- (SOM), and vasoactive intestinal peptide- (VIP) INs. Studies in mouse lines expressing Cre-recombinase in each of these IN classes are rapidly revealing distinct patterns of connectivity, response properties and in vivo function for each class. However, it remains unknown whether insights gained from mouse cortex apply to cortical INs in primates and humans. IN dysfunction in humans has been implicated in several disorders, such as epilepsy, schizophrenia, anxiety and autism, therefore it is important to understand normal cortical IN connectivity and function in primates. The lack of viral tools to selectively access IN subtypes, and the difficulty of performing genetic manipulations in primates have been major impediments to studying INs in this animal model. Our goal is to leverage recent advances in the development of viral tools to express transgenes in specific INs subtypes to investigate the connectivity, response properties, and computational function of two major classes of INs, PV and SOM, in the superficial layers of the primate primary visual cortex (V1). Using IN-type specific expression of Cre-recombinase combined with rabies-virus monosynaptic circuit tracing, we will map local and brain-wide inputs to specific V1 IN classes (Aim1). Using two-photon imaging of IN-type specific targeted calcium indicators, or optogenetic identification of channelrhodopsin-tagged IN types, we will characterize the visual response properties of distinct V1 IN classes (Aim2). Finally, we will use optogenetic inactivation of distinct IN-types expressing inhibitory opsins, to understand the relative roles of IN classes in V1 computations (Aim3). We will test specific hypotheses derived from available data in mouse, the specific geometry of PV and SOM cells in primate cortex, published computational models of feature tuning and surround suppression in visual cortex, and our preliminary results. Impact. The proposed studies will provide the first account of the connectivity, visual properties and computational function of PV and SOM INs in primate cortex, paving the way for studies of IN function in this order. They will also reveal conserved principles of IN function across species, as well as fundamental inter- species differences, stressing the importance of studying cortical function in species that are evolutionarily closer to humans.

项目总结