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Solving the Valence Assignment Problem

解决化合价分配问题

基本信息

批准号：
10577827
负责人：
Kay Maxine Tye
金额：
$ 93.8万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10577827
关键词：
Affect Amygdaloid structure Animals Anxiety Architecture Association Learning Attenuated Behavior Behavioral Bipolar Disorder Brain Cell surface Cells Chemosensitization Clustered Regularly Interspaced Short Palindromic Repeats Code Cues Data Discrimination Electrophysiology (science)Fright Funding G-Protein-Coupled Receptors Genes Geniculate body structure Glutamates Goals Hippocampus Impairment Learning Long-Term Potentiation Maintenance Medial Mediating Mental Depression Mental disorders Modeling Mus Negative Valence Neuromodulator Neurons Neuropeptides Neurotensin Noise Outcome Output Pathologic Play Positioning Attribute Positive Valence Prevalence Property Punishment Research Rewards Role Schizophrenia Signal Transduction Site Source Stimulus Surface Synapses System Testing Textbooks Thalamic structure Time Ventral Nuclear Group Vision Work Writing addiction antagonist differential expression druggable target effective therapy glutamatergic signaling in vivo knock-down memory retrieval nerve supply neural neural circuit neuroregulation neurotensin type 1 receptor novel novel strategies novel therapeutics optogenetics parallel processing pharmacologic postsynaptic receptor response self-directed learning side effect therapeutic development transcriptome transmission process

项目摘要

PROJECT SUMMARY The ability to discriminate between what is “good” and “bad” is termed valence processing, and pathological perturbations in valence processing can explain mental health disorders ranging from anxiety and depression to compulsivity and bipolar disorder. The key to developing more effective treatments for mental health disorders with fewer side-effects will be in the synaptic, cellular, and circuit mechanisms. This proposal not only lays out a very specific research plan to probe the functional role of a neuropeptide, neurotensin (NT), but it also lays out a comprehensive, systematic approach to investigating neuromodulatory systems. The general approach includes: 1) Identify a circuit that plays a causal and critical role in valence processing, 2) Profile the transcriptome of this circuit component, 3) Select for surface receptors or other druggable targets, 4) Determine the contribution of this neuromodulatory signal on plasticity, 5) Establish the input-output architecture of the neuromodulatory innervation and postsynaptic, downstream targets, and 6) Establish a causal role for this particular neuromodulatory signal in neural activity and behavior associated with valence processing. The specific hypotheses included in this proposal are: that NT serves to guide plasticity to the appropriate target, that there are parallel circuits that have some local interaction in the BLA, and that NT alters the coding dynamics by increasing signal-to-noise ratio by amplifying signal by modulation of glutamatergic transmission. A successful outcome of this project will provide a specific model for how a neuromodulatory signal such as NT can solve the “valence assignment problem.”

项目总结