Synaptic mechanisms of temporal pattern recognition

描述（由申请人提供）：本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与行为相关的线索。刺激的时间几乎在每一种感觉形态中都携带着信息。例如，声音的时间线索对人类语音感知（如音高和音素辨别）的各个方面至关重要。此外，时间模式也可能在一种被称为新颖性检测的现象中发挥作用，或者识别新的感官刺激。时间和新奇线索听觉加工的中断与阅读障碍、中枢性听觉加工障碍和自闭症有关。在听觉和电感觉中，时间线索的解码是由中脑神经元对连续刺激之间的时间间隔进行调整。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。一些假设试图描述神经回路如何建立区间调谐和新颖性检测，但这些假设的核心兴奋和抑制的潜在行为仍然不确定。结合尖端的电生理学和计算方法，本提案将确定在弱电鱼的电感觉中脑神经元中产生间隔调谐和新颖性检测的兴奋性和抑制性输入的相互作用。目的1将确定短期突触可塑性的兴奋和抑制在建立间隔调谐中的作用。在不同的电流注射水平下，收集不同刺激间隔的感觉刺激期间的体内全细胞膜片钳记录。接下来，将计算每个神经元反应背后的兴奋性和抑制性突触传导，以揭示短期抑制和/或促进如何有助于产生间隔调谐。最后，将兴奋性和抑制性输入的时间常数和可塑性强度变化到模式泄漏整合-火神经元上，并测量模型神经元对变间隔刺激的反应。这些方法将验证间隔调谐可能是由兴奋和抑制通路的抑制时间过程的差异引起的假设。目的2将确定短期突触可塑性在检测新刺激中的作用。Aim 1中使用的电生理学和计算方法将用于揭示当神经元受到由常见（更频繁）和罕见（更不频繁）刺激脉冲组成的刺激序列时的兴奋和抑制行为。在相同的刺激下，我们将测量不同的塑性兴奋和抑制的时间过程对模型泄漏整合-火神经元的影响。这些方法将验证一个假设，即经历短期兴奋抑制的神经元子集将能够检测到新的刺激。这一建议的结果将提供突触机制的描述，由中央电路用于处理时间信息在社会交流途径，并进一步我们的理解神经基础的几种疾病。

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.