Solving the Valence Assignment Problem

解决化合价分配问题

基本信息

批准号：
10388233
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/10388233
关键词：
Affect Amygdaloid structure Animals Anxiety Architecture Attenuated Behavior Behavioral Bipolar Disorder Brain Cell surface Cells Chemosensitization Clustered Regularly Interspaced Short Palindromic Repeats Code Cues Data Discrimination Electrophysiology (science)Fright Fruit Funding G-Protein-Coupled Receptors Genes Geniculate body structure Glutamates Goals Hippocampus (Brain)Impairment Learning Long-Term Potentiation Maintenance Medial Mediating Mental Depression Mental disorders Modeling Mus Negative Valence Neuromodulator Neurons Neuropeptides Neurotensin Neurotensin Receptors Noise Outcome Output Pathologic Pharmacology 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 Vision Work addiction antagonist classical conditioning differential expression druggable target effective therapy glutamatergic signaling in vivo knock-down memory retrieval nerve supply neural circuit neuroregulation novel novel strategies novel therapeutics optogenetics parallel processing postsynaptic receptor relating to nervous system response self-directed learning side effect therapeutic development transcriptome transmission process

Affect Amygdaloid structure Animals Anxiety Architecture Attenuated Behavior Behavioral Bipolar Disorder Brain Cell surface Cells Chemosensitization Clustered Regularly Interspaced Short Palindromic Repeats Code Cues Data Discrimination Electrophysiology (science)Fright Fruit Funding G-Protein-Coupled Receptors Genes Geniculate body structure Glutamates Goals Hippocampus (Brain)Impairment Learning Long-Term Potentiation Maintenance Medial Mediating Mental Depression Mental disorders Modeling Mus Negative Valence Neuromodulator Neurons Neuropeptides Neurotensin Neurotensin Receptors Noise Outcome Output Pathologic Pharmacology 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 Vision Work addiction antagonist classical conditioning differential expression druggable target effective therapy glutamatergic signaling in vivo knock-down memory retrieval nerve supply neural circuit neuroregulation novel novel strategies novel therapeutics optogenetics parallel processing postsynaptic receptor relating to nervous system response self-directed learning side effect therapeutic development transcriptome transmission process

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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.”

项目摘要区分“好”和“坏”的能力称为价加工和价值处理中的病理扰动可以解释心理从焦虑和抑郁到强迫性和双极性的健康障碍紊乱。开发更有效治疗精神疾病的关键在突触，细胞和电路机制中，副作用较少。该提案不仅制定了一个非常具体的研究计划来探讨功能作用神经肽（NT）的神经肽，但它也提出了全面的，系统的研究神经调节系统的方法。一般方法包括：1）确定扮演因果关系和关键作用的电路在价处理中，2）介绍该电路组件的转录组，3）选择对于表面受体或其他可药物靶标，4）确定此的贡献神经调节信号可塑性，5）建立的输入架构神经调节神经和突触后，下游靶标，6）建立这种特定神经调节信号在神经活性和行为中的因果作用与价处理相关。该提案中包括的特定假设是：NT用于指导可塑性对于适当的目标，有一些平行电路具有某些局部交互在BLA中，NT通过增加信噪比来改变编码动力学通过通过调节谷氨酸能传输来扩增信号。该项目的成功结果将为如何提供一个特定的模型 NT之类的神经调节信号可以解决“价分配问题”。