Circuit and synaptic basis of cognitive control in monkey prefrontal cortex

猴前额皮质认知控制的回路和突触基础

基本信息

批准号：
9263766
负责人：
MATTHEW V CHAFEE
金额：
$ 31.12万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9263766
关键词：
Action Potentials Acute Affect Anatomy Behavior Control Behavioral Brain Chronic Chronic Schizophrenia Code Cognition Cognitive Communication Computer Analysis Coupled Coupling Data Event Failure Functional disorder Goals Human Impaired cognition Impairment Knowledge Lead Learning Linear Models Link Measures Mediating Monkeys Motor Motor output N-Methyl-D-Aspartate Receptors NMDA receptor antagonist Neurons Parietal Parietal Lobe Pathogenesis Patients Pattern Performance Pharmaceutical Preparations Pharmacology Physiological Population Prefrontal Cortex Primates Process Research Schizophrenia Sensory Signal Transduction Stimulus Synapses Task Performances Testing Time Training base behavioral response cognitive control cognitive performance information processing innovation multi-electrode arrays neural circuit neuropsychiatric disorder neuropsychiatry novel operation public health relevance receptor function relating to nervous system response sensory input synaptic function theories transmission process

项目摘要

DESCRIPTION (provided by applicant): The objective of this proposal is to characterize the circuit basis of cognitive control in monkey prefrontal cortex, and to learn how a specific failure of circuit dynamics can lead to errors in cognitive control that are very much like those seen in several human neuropsychiatric diseases, including schizophrenia. To evaluate functional interactions between neurons in circuits, we will combine large scale, single neuron recording in prefrontal and parietal cortex simultaneously while monkeys perform the same cognitive control task used to measure cognitive impairment in neuropsychiatric patients. This will provide many sets of simultaneously recorded neurons (each containing ~40-60 neurons). Prefrontal and parietal cortex are anatomically connected and both contribute to cognitive control. We will then analyze temporal relationships in the spike trains of simultaneously recorded neurons to detect patterns of functional coupling between them. We will infer that neurons are functionally coupled in cases that the timing of their action potentials, or fluctuations in the behavioral information they encode, covary between neurons over time on a rapid time scale. To measure these interactions, we develop and apply two novel analytical approaches that quantify functional coupling between neurons both in terms of spike times and coded information. We then relate patterns of functional coupling between neurons to specific information processing operations required by the task. This provides a basis to relate synaptic function to computation in prefrontal circuits. Next we will block NMDA receptors (NMDAR) in monkeys using a systemically administered drug. This will induce a transient period of cognitive impairment in monkeys, during which time they will make a specific pattern of errors in task performance that is nearly identical to the error pattern of patients with schizophrenia performing the same task. Neural recording during the cognitive impairment will allow us to relate changes in functional coupling to errors in performance. We will test the hypotheses that: (a) computations for cognitive control are mediated by information transfer between neurons in prefrontal circuits, (b) this transmission is mediated by precise control of the timing of action potentials in communicating neurons, (c) action potential timing in communicating neurons is strongly influenced by NMDA receptors, (d) loss of NMDAR synaptic function distorts activity timing relationships between neurons, (e) this causes loss of information transfer between neurons, (f) leading to cognitive control failure. By establishing this chain of events, from synapses through circuits to cognition, we will relate a very specific pattern of cognitive failure seen in neuropsychiatric disease to a causal cortical circuit failure.

描述（申请人证明）：这是表征Monkefrontal EX中认知控制的电路基础的目的，并了解特定失败电路动力学可以导致控制，就像在几个人类神经精神疾病中看到的那些人，以评估在电路中的功能相互作用，我们将同时结合大规模的TAL Cortex s的s同时记录了神经元（〜40-60个神经元）。他们的作用的时间或行为上的波动hey编码，随着时间的流逝，神经元之间的co纳在快速的时间范围内，我们开发并应用了两种新型的分析方法，以量化神经元之间的功能耦合。然后，我们将神经元之间的功能耦合模式与任务所需的特定信息操作相关联。 . Ent in MONKEYS, DURING TICH TIME THEY WILL MATTERN ON TASK PERFORMANCE THAT ISK PERFORMANCE TO THE ERROROROR PATTERN OFFITH WITH IZOPHRENIA PERFORMING THE SAME TASK. NEURAL Recording During The Cognitive Impairment Will Allow Us To Relate Changes in Functional Coupling to Errrrrrrrrrrrrrrrrrrrrrors In Performance. We将检验以下假设：（a）l电路，（b）这种传播是通过对通信神经元中动作电位的精确控制来介导的（C沟通的动作电位时机受神经元之间NMDA受体关系的强烈影响（（（ e）这是神经元之间的信息传递的原因，（f）通过建立这一事件导致认知控制失败，我们将在N欧洲精神病中将非常具体的认知衰竭模式与因果皮质回路失败联系起来。