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CRCNS: Odor processing by cortical neural circuits

CRCNS：皮质神经回路的气味处理

基本信息

批准号：
9472416
负责人：
Kevin Franks
金额：
$ 17.91万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9472416
关键词：
Address Affect Alzheimer&apos s Disease Amygdaloid structure Anhedonia Architecture Area Automobile Driving Back Behavior Biological Models Brain Cells Characteristics Computer Simulation Data Dementia Dependence Discrimination Disease Dissection Electrophysiology (science)Environment Epilepsy Experimental Models Functional disorder Goals Heterogeneity Image In Vitro Individual Label Measures Mediating Mental Depression Minor Modeling Molecular Molecular Genetics Morphology Mus Neurons Odors Olfactory Cortex Parkinson Disease Pattern Physiology Play Population Process Property Pyramidal Cells Research Personnel Role Schizophrenia Shapes Specific qualifier value Specificity Stimulus Stream Structure Synapses Synaptic plasticity System Testing Update awake cell type experimental study frontal lobe human morbidity human mortality in vivo in vivo imaging in vivo two-photon imaging insight multidisciplinary network models neural circuit olfactory bulb piriform cortex relating to nervous system response sensory input sensory system tool

项目摘要

Project Summary The enormous diversity of neural cell types is a defining characteristic of the brain. Different neural circuits consist of a myriad of distinct cell types, each with specific intrinsic properties and patterns of synaptic connectivity, which transform neural input and convey this information to downstream targets. However, despite their fundamental importance in neural processing, our understanding of how individual cell types differentially contribute to neural circuit function and computation remains poor. Here, the investigators leverage a highly tractable neural circuit, the mouse olfactory (piriform, PCx) cortex, to determine how information about odor stimuli is encoded, transformed, and conveyed to its different downstream target areas. The objective of this proposal is to register diverse odor responses observed in PCx neurons onto identified neural cell types, defined by their morphology, intrinsic properties, and connectivity. This will be achieved via a collaborative, multidisciplinary, iterative computational-experimental approach, involving computational modeling, in vivo two photon imaging, in vitro electrophysiology, behavior, chemogenetics and decoding analyses. The investigators' working hypothesis is that different features of an odor - its identity, intensity, and valence - are selectively extracted and encoded by distinct subsets of PCx neurons by virtue of their different intrinsic and local circuit properties, and then selectively transmitted to different target areas. In the two aims proposed, the investigators will image activity evoked by different odorants at multiple concentrations in subpopulations of PCx neurons in awake, behaving mice. They will compare their imaging data with simulated odor-evoked activity in a computational model in which they incorporate the specific intrinsic properties and patterns of local synaptic connectivity of these subpopulations of PCx neurons. In Aim1, the investigators will image and model odor responses in two morphologically distinct subtypes of principal neurons, semilunar cells and superficial pyramidal cells. In Aim 2 they use a similar approach, but with subpopulations of PCx neurons defined by their specific projection targets. Mice will be performing a go/no go odor discrimination task during imaging, allowing characterization of responses to odors with different identities, concentrations or valence. This experimental-computational approach will determine the extent to which the distinct intrinsic properties and specific connectivity patterns of different cell-types accounts for differences in their odor responses. Crucially, mismatches between modeling and experimental results will reveal additional properties of these cells and circuitry that may determine their odor responses, which can and will be tested experimentally. Achieving the goals of this proposal will therefore provide a coherent framework for understanding how different features of an odor stimulus can be selectively extracted, encoded and conveyed to appropriate downstream targets.

项目总结