Synaptic mechanisms of temporal pattern recognition

时间模式识别的突触机制

• 批准号: 8452363
• 负责人: Christa A Baker
• 金额: $ 2.85万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8452363
• 关键词: Affect; Afferent Neurons; Auditory; Autistic Disorder; Behavior; Biological Models; Brain; Cells; Central Auditory Processing Disorder; Cochlear Implants; Code; Communication; Complex; Comprehension; Computer Simulation; Computing Methodologies; Cues; Data; Detection; Discrimination; Disease; Dyslexia; Electric Fish; Elements; Excitatory Synapse; Fire - disasters; Fishes; Functional disorder; Generations; Goals; Human; In Vitro; Individual; Injection of therapeutic agent; Knowledge; Measurement; Measures; Mental Depression; Methods; Midbrain structure; Modality; Modeling; Neural Pathways; Neurons; Output; Pathway interactions; Pattern; Pattern Recognition; Perception; Physiologic pulse; Pitch Perception; Plastics; Play; Process; Property; Relative (related person); Research; Role; Schizophrenia; Sensory; Sensory Process; Slice; Speech; Speech Perception; Stimulus; Synapses; Synaptic plasticity; System; Techniques; Testing; Time; Training; Variant; Whole-Cell Recordings; auditory stimulus; base; career; detector; experience; in vivo; insight; neural circuit; novel; operation; patch clamp; presynaptic; relating to nervous system; research study; response; sensory stimulus; sensory system; social communication; sound; synaptic depression; time interval

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to understand how sensory circuits in the brain extract behaviorally relevant cues from information contained within a timing code. The timing of stimuli carries information in almost every sensory modality. For example, the timing cues of sounds are critical for aspects of human speech perception such as pitch and phoneme discrimination. Further, timing patterns may also play a role in a phenomenon called novelty detection, or the identification of a new sensory stimulus. Disruptions in the auditory processing of timing and novelty cues have been implicated in dyslexia, Central Auditory Processing Disorder, and autism. In audition and electrosensation, the decoding of timing cues is performed by midbrain neurons tuned to the time intervals between successive stimuli. Additionally, single-neuron novelty detectors have been found in mammalian auditory and fish electrosensory pathways. Several hypotheses attempt to describe how neural circuits can establish interval tuning and novelty detection, but the underlying behaviors of excitation and inhibition central to these hypotheses remain uncertain. Using a combination of cutting-edge electrophysiological and computational methods, this proposal will identify the interactions of excitatory and inhibitory inputs that produce interval tuning and novelty detection in electrosensory midbrain neurons of weakly electric fish. Aim 1 will determine the role of short-term synaptic plasticity of excitation and inhibition in establishing interval tuning. In vivo whole-cell patch clamp recordings during sensory stimulation with varying interstimulus intervals will be collected at different levels of current injection. Next, the excittory and inhibitory synaptic conductances underlying each neuron's responses will be calculated to reveal how short-term depression and/or facilitation contribute to producing interval tuning. Finally, the time constant and strength of plasticity of excitatory and inhibitory inputs onto mode leaky integrate-and-fire neurons will be varied and the response of the model neurons to varying-interval stimulation measured. These methods will test the hypothesis that interval tuning can result from differences in the time course of depression of excitatory and inhibitory pathways. Aim 2 will determine the role of short-term synaptic plasticity in detecting novel stimuli. The electrophysiological and computational methods employed in Aim 1 will be used to reveal the behavior of excitation and inhibition when a neuron is presented with a stimulus train consisting of common (more frequent) and rare (less frequent) stimulus pulses. The effect of varying the time courses of plastic excitation and inhibition onto model leaky integrate-and-fire neurons in response to the same stimuli will be measured. These methods will test the hypothesis that a subset of neurons that experience short-term depression of excitation will be able to detect novel stimuli. The results of this proposal will provide a description of the synaptc mechanisms employed by central circuits for the processing of timing information in a social communication pathway as well as further our understanding of the neural basis of several disorders. PUBLIC HEALTH RELEVANCE: This project holds relevance for understanding fundamental neural processes involved in sensory processing, and may provide insight into the dysfunction of neural circuits in conditions such as dyslexia, Central Auditory Processing Disorder, autism, and schizophrenia. A thorough knowledge of how intact neural pathways perform operations critical for sensory perception is vital to research that seeks to identify the underlying causes o complex human disorders.

描述（由申请人提供）：该提案的长期目标是了解大脑中的感觉回路如何从计时代码中包含的信息中提取行为相关线索。刺激的时间几乎在每一种感觉形态中都携带着信息。例如，声音的时间线索对于人类语音感知的各个方面（如音高和音素辨别）至关重要。此外，定时模式也可以在称为新奇检测的现象中发挥作用，或者识别新的感官刺激。听觉处理时间和新奇线索的中断与阅读障碍、中枢听觉处理障碍和自闭症有关。在听觉和电感觉中，时间线索的解码是由中脑神经元执行的，这些神经元被调谐到连续刺激之间的时间间隔。此外，在哺乳动物的听觉和鱼类的电感觉通路中也发现了单神经元新奇探测器。一些假说试图描述神经回路如何建立间隔调谐和新奇检测，但这些假说的核心兴奋和抑制的基本行为仍然不确定。使用尖端的电生理学和计算方法相结合，该建议将确定的兴奋性和抑制性输入的相互作用，产生间隔调谐和新奇检测在电感觉中脑神经元的弱电鱼。目的1将确定兴奋和抑制的短时程突触可塑性在建立间隔调谐中的作用。将在不同的电流注入水平下收集感觉刺激期间具有不同刺激间间隔的体内全细胞膜片钳记录。接下来，兴奋性和抑制性突触电导的基础上每个神经元的反应将被计算，以揭示如何短期抑郁症和/或促进有助于产生间隔调谐。最后，将改变对模式泄漏的整合和发射神经元的兴奋性和抑制性输入的可塑性的时间常数和强度，并测量模型神经元对变化间隔刺激的响应。这些方法将测试的假设，间隔调谐可以导致兴奋性和抑制性通路的抑郁症的时间过程中的差异。目的2将确定短期突触可塑性在检测新刺激中的作用。目标1中采用的电生理学和计算方法将用于揭示当神经元呈现由常见（更频繁）和罕见（更少频率）刺激脉冲组成的刺激序列时的兴奋和抑制行为。将测量改变可塑性激发和抑制的时程对响应于相同刺激的模型渗漏整合和激发神经元的影响。这些方法将测试这样一个假设，即经历短期抑制兴奋的神经元子集将能够检测到新的刺激。这个建议的结果将提供一个描述的synaptc机制所采用的中央电路的处理定时信息的社会沟通途径，以及进一步我们的理解的神经基础的几种疾病。 公共卫生关系：该项目与理解感觉处理中涉及的基本神经过程相关，并可能提供对阅读障碍，中枢听觉处理障碍，自闭症和精神分裂症等条件下神经回路功能障碍的见解。完整的神经通路如何执行对感官知觉至关重要的操作的透彻了解，对于寻求确定复杂人类疾病的根本原因的研究至关重要。