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|通过轨道额皮层电路对关联学习的神经编码眶额皮层（OFC）的功能障碍可能引起冲动的决策，并与神经精神疾病包括成瘾，强迫症，重度抑郁症，注意力赤字多动障碍和精神分裂症。然而，OFC神经回路的功能以及它们如何与这些疾病的障碍关系尚不清楚。冲动决策的特征是无法根据他们的预测结果来优化决策。因此，它可能是由于两个帕夫洛维亚人的功能障碍而产生的学习刺激结果关联和工具系统的系统，这些系统学习刺激性能 - 结果协会。 OFC被认为传达了这两种类型的关联，包括腹侧细分区域（VTA） - 学习的关键调节器。那样，冲动的决策可能是 OFC内这些学习系统中的差异畸变。因此，了解这些关联的方式由OFC神经回路学习和维护的可能是揭示其在健康方面的功能和疾病。要了解遗传或投影定义的神经元如何学习和维护信息，这是必须纵向跟踪学习期间和学习之后的活动的演变。最新的成像和遗传/病毒方法现已使这成为可能。使用这些技术，我提出了试点数据证明我已经纵向跟踪了数千个OFC神经元的活动，包括随着小鼠学习刺激与奖励之间的关联，投影给VTA。但是，这项活动是否这些实验中发现的模式将中继到其他地方的OFC输出神经元，或者是一个局部计算的产物尚不清楚。因此，我首先提出了研究内侧丘脑的输入，一个所显示的用于编码关联信息的结构由OFC电路集成以影响输出活动。作为该目标的一部分，我将训练以建立功能性的第一个目的进行贴片钳电生理学该输入与OFC内的特定和投影定义的细胞类型的连接性。在第二个目的，我将在纵向跟踪响应时光学上沉默的丘脑内侧丘脑通道。在学习刺激 - 奖励关联过程中VTA投射的VTA投射的演变。最后，我建议过渡我的独立研究，以研究OFC中的特定细胞类型如何学习工具关联到通过延迟的折扣任务来指导决策，通常用于衡量冲动性。给了我的毕业生对大鼠工具行为和跨期决策的理论背景进行培训，这些拟议的目标将帮助我建立独特的研究线。此外，技术和管理培训聚集在K99阶段，以及我的咨询委员会和机构的支持，将帮助我过渡在学术研究中成为独立的教师职位。

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。