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Neural encoding of associative learning by orbitofrontal cortex circuits

眶额皮层回路联想学习的神经编码

基本信息

批准号：
10458666
负责人：
Vijay Mohan K Namboodiri
金额：
$ 24.9万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
2020-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458666
关键词：
Address Advisory Committees Affect Animals Anxiety Attention deficit hyperactivity disorder Axon Behavior Behavioral Brain Cues Data Decision Making Disease Distal Electrophysiology (science)Elements Evolution Faculty Functional disorder Future Goals Head Health Image Impairment Impulsivity Institution Interneurons Learning Light Major Depressive Disorder Maps Measures Medial Mediating Methods Mus Nature Neurons Obsessive compulsive behavior Obsessive-Compulsive Disorder Operant Conditioning Outcome Output Parvalbumins Pathway interactions Pattern Phase Positioning Attribute Prefrontal Cortex Rattus Research Rest Rewards Role Schizophrenia Somatostatin Stimulus Structure Synapses System Techniques Thalamic structure Training Ventral Tegmental Area addiction base cell type classical conditioning discounting experimental study flexibility imaging genetics insight neural circuit neuropsychiatric disorder optogenetics outcome prediction patch clamp relating to nervous system response virus genetics

项目摘要

Project Summary/Abstract | Neural encoding of associative learning by orbitofrontal cortex circuits Dysfunction of the orbitofrontal cortex (OFC) can cause impulsive decision-making, and is implicated in neuropsychiatric disorders including addiction, obsessive compulsive disorder, major depression, attention deficit hyperactivity disorder and schizophrenia. Nevertheless, the function of OFC neural circuits, and how their impairment relates to these disorders is unknown. Impulsive decision-making is characterized by an inability to optimize decisions based on their predicted outcome. It may thus arise due to the dysfunction of both Pavlovian systems, which learn stimulus-outcome associations, and instrumental systems, which learn stimulus-action- outcome associations. OFC is thought to convey both these types of associations, including to the ventral tegmental area (VTA)—a key regulator of learning. Thus, impulsive decision-making may be a consequence of differential aberrations in these learning systems within OFC. Hence, understanding how these associations are learned and maintained by OFC neural circuits may be fundamental to unraveling its function in health and disease. To understand how genetically or projection-defined neurons learn and maintain information, it is imperative to longitudinally track the evolution of their activity during and after learning. Recent state-of-the-art imaging and genetic/viral methods have now made this possible. Using these techniques, I present pilot data demonstrating that I have longitudinally tracked the activity of thousands of OFC neurons, including those projecting to VTA, as mice learned the associations between stimuli and rewards. However, whether the activity patterns uncovered in these experiments are relayed onto these OFC output neurons from elsewhere, or are a product of local computation is unknown. Hence, I first propose to study how input from the medial thalamus, a structure shown to encode associative information, is integrated by the OFC circuit to affect output activity. As part of this goal, I will train to perform patch-clamp electrophysiology in the first aim to establish functional connectivity of this input with specific genetically and projection-defined cell types within OFC. In the second aim, I will optogenetically silence the medial thalamus-to-OFC pathway while longitudinally tracking response evolution of VTA projecting OFC neurons during the learning of stimulus-reward associations. Lastly, I propose to transition my independent research to study how specific cell-types in OFC learn instrumental associations to guide decision-making, through a delay discounting task often used to measure impulsivity. Given my graduate training in rat instrumental behavior and theoretical background in intertemporal decision-making, these proposed aims will help me establish a unique line of research. Further, the technical and managerial training gathered during the K99 phase, and the support of my advisory committee and institution, will help me transition to an independent faculty position in academic research.

项目摘要/摘要|眶额皮质回路对联想学习的神经编码

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

How do real animals account for the passage of time during associative learning?

DOI：
10.1037/bne0000516
发表时间：
2022-10
期刊：
Behavioral neuroscience
影响因子：
1.9
作者：
Namboodiri VMK
通讯作者：
Namboodiri VMK

Few-shot learning: temporal scaling in behavioral and dopaminergic learning.

少样本学习：行为和多巴胺能学习中的时间尺度。

DOI：
10.1101/2023.03.31.535173
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Burke,DennisA;Jeong,Huijeong;Wu,Brenda;Lee,SeulAh;Floeder,JosephR;Namboodiri,VijayMohanK
通讯作者：
Namboodiri,VijayMohanK

Sensory cortical ensembles exhibit differential coupling to ripples in distinct hippocampal subregions.

感觉皮层整体表现出与不同海马亚区域波纹的差异耦合。