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Characterizing the Functional Architecture of the Necklace Olfactory System

表征项链嗅觉系统的功能架构

基本信息

批准号：
9333141
负责人：
Sandeep R Datta
金额：
$ 49.77万
依托单位：
HARVARD MEDICAL SCHOOL
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：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9333141
关键词：
Address Afferent Neurons Animals Architecture Area Arousal Attention Behavior Behavioral Brain Brain region Carbon Characteristics Chemicals Cues Data Detection Discrimination Disulfides Environment Esthesia Evolution Family Food Food Preferences Future G-Protein-Coupled Receptors Gene Cluster Genetic Genetic screening method Goals Guanylate Cyclase Individual Learning Ligands Mammals Mediating Membrane Modality Modernization Mus Mutate Neurobiology Neurons Nose Odors Olfactory Pathways Output Pathologic Pathway interactions Pattern Peptides Peripheral Pheromone Physiology Play Process Receptor Gene Role Sensory Smell Perception Stimulus Structure Synapses System Techniques Testing Variant Vomeronasal Systems Work basal forebrain base brain cell cell type cholinergic neuron design detector experimental study improved in vivo information processing insight intimate behavior mammalian genome neural circuit neuromechanism neuroregulation novel olfactory bulb optogenetics piriform cortex receptor relating to nervous system response sensory input social tool transmission process urinary

项目摘要

Abstract A central goal of modern neurobiology is to understand the neural mechanisms that transform sensory inputs from the outside world into appropriate and adaptive behavioral outputs. Here we propose to approach this general problem by answering key questions regarding the organization and function of the olfactory system, the main sensory modality used by most animals to interrogate the environment. In mammals, the challenge of odor detection is addressed by multiple olfactory subsystems that each convey information about a unique subset of odor space. In the two largest olfactory subsystems — the main and the vomeronasal systems — sensory neurons detect odors through g-protein coupled receptors (GPCRs) expressed in a characteristic one-receptor-per-neuron pattern; odor information is then organized into channels called glomeruli in the olfactory bulb, and is relayed to higher brain centers responsible for odor processing and behavior. However, not all olfactory subsystems follow this pattern: the mysterious olfactory “necklace” is comprised of sensory neurons that innervate a string of glomeruli in the olfactory bulb, and which express the single-pass transmembrane receptor guanylate cyclase-D (GC-D) rather than GPCRs. GC-D detects chemical cues, including urinary peptides and carbon disulfide, that act as unconditioned stimuli during a specific form of odor learning, the social transmission of food preferences (STFP). We have recently identified a new family of 4 transmembrane-containing odor receptors called the Membrane Spanning 4As (MS4As), which are co- expressed in necklace sensory neurons, and which detect odors ranging from food scents to pheromones. This co-expression of non-GPCR odor receptors in necklace sensory neurons suggests that the necklace system plays a fundamentally different role in olfactory perception from the discriminative functions for which the main and vomeronasal systems appear to be optimized. Here we will take advantage of new genetic tools we have established, and novel neural tracing and behavioral techniques we have developed, to tease apart the unique function of the necklace system in odor perception and behavior. We will first assess necklace sensory responses in mice in which single Ms4a receptor genes are mutated or the entire Ms4a gene cluster is deleted, and also ask whether MS4A and GC-D ligands, when presented simultaneously, activate necklace sensory neurons synergistically, additively or in some other pattern (Aim I). We will then perform anterograde and retrograde tracing (including cell type-specific trans-synaptic tracing) to identify brain areas and cell types that receive information from the necklace system (Aim II). Finally, we will use genetics and optogenetics to manipulate the necklace system, thereby establishing the roles of MS4A ligands, receptors and projections from the necklace glomeruli to the brain in STFP-based odor learning. These experiments will lead to important discoveries about the functional architecture of a behaviorally relevant neural circuit, and will establish an important platform for testing future hypotheses about the mechanisms that couple sensation to action.

摘要