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

• 批准号: 8943506
• 负责人: MATTHEW V CHAFEE
• 金额: $ 31.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 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/8943506
• 关键词: Action Potentials; Acute; Affect; Behavior Control; Behavioral; Brain; Chronic; Code; Cognition; Cognitive; Communication; Coupled; Coupling; Data; Disease; 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; Physiological; Population; Prefrontal Cortex; Primates; Process; Relative (related person); Research; Schizophrenia; Sensory; Shapes; Signal Transduction; Stimulus; Synapses; Task Performances; Testing; Time; Training; base; behavior influence; behavioral response; cognitive control; cognitive performance; information processing; innovation; multi-electrode arrays; neural circuit; neuropsychiatry; novel; operation; public health relevance; receptor function; relating to nervous system; response; sensory input; synaptic function; theories; transmission process

 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（由适用提供）：该提案的目的是表征猴前额叶皮层认知控制的电路基础，并了解特定失败 电路动力学可能会导致认知控制中的错误，就像在包括精神分裂症在内的几种人类神经精神疾病中所见的那样。为了评估电路中神经元之间的功能相互作用，我们将简单地结合大规模的，单神经元记录的单个神经元记录，而猴子执行与测量神经精神病患者认知障碍相同的认知控制任务。这将提供许多易于记录的神经元（每个神经元）。前额叶和顶叶皮层在解剖上连接，都有助于认知控制。然后，我们将分析易于记录的神经元的尖峰列车中的临时关系，以检测它们之间的功能耦合模式。我们将推断神经元在其作用电位的时机或它们所编码的行为信息的波动（随时间范围内神经元之间的co缩合）的情况下，在功能上是耦合的。为了衡量这些相互作用，我们开发并应用了两种新型的分析方法，这些方法在峰值时间和编码信息方面都量化神经元之间的功能耦合。然后，我们将神经元之间功能耦合的模式与任务所需的特定信息处理操作相关联。这提供了将突触功能与前额叶电路中的计算相关联的基础。接下来，我们将使用系统施用的药物阻止猴子中的NMDA受体（NMDAR）。这将引起猴子的瞬时认知障碍时期，在此期间，他们将在任务绩效中的特定错误模式，这几乎与精神分裂症患者执行相同任务的患者的错误模式几乎相同。认知障碍期间的神经记录将使我们能够将功能耦合的变化与性能错误联系起来。 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）这会导致神经元之间的信息传递丧失，（f）导致认知控制失败。通过建立从突触到电路到认知的这一事件链，我们将将在神经精神疾病中看到的非常具体的认知失败模式与因果皮质回路衰竭联系起来。