Multiple roles of inhibition in temporal coding of sensory information

抑制在感觉信息时间编码中的多重作用

• 批准号: 8260386
• 负责人: Ariel Maia Lyons-Warren
• 金额: $ 4.72万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260386
• 关键词: Address; Affect; Anterior; Auditory; Axon; Biological Models; Birds; Brain; Cell Nucleus; Cells; Central Auditory Processing Disorder; Code; Data; Discrimination; Ear; Electric Fish; Electric Organ; Electrodes; Electron Microscopy; Electrophysiology (science); Event; Evoked Potentials; Exhibits; Fellowship; Fire - disasters; Fishes; Fluorescent Dyes; Functional disorder; Goals; Histologic; Human; Immunohistochemistry; Individual; Inherited; Inhibitory Synapse; Length; Location; Mammals; Measures; Mediating; Midbrain structure; Modality; Modeling; Mormyridae; Neuraxis; Neurons; Output; Pattern; Perception; Physiologic pulse; Population; Process; Property; Relative (related person); Research; Research Personnel; Role; Sensory; Sensory Process; Shapes; Signal Transduction; Sound Localization; Speech; Stimulus; Synaptic Potentials; System; Testing; Time; Training; Vertebrates; base; brain cell; extracellular; improved; in vivo; insight; interest; millisecond; neural circuit; neuronal cell body; novel; oral communication; relating to nervous system; research study; response; sound; spatial integration; time use

DESCRIPTION (provided by applicant): The objective of this proposal is to identify specific mechanisms governing the role of inhibition in temporal coding. A temporal code uses precisely timed events to represent information. For example, sound localization in birds, mammals, and other vertebrates relies on temporal codes in which the events are spike times. In this case, neurons first fire spikes at specific times relative to the time at which the sound arrives at each ear. Then, time-comparing neurons integrate those spike times such that specific cells only respond when sound comes from certain locations. Temporal coding is also important for recognizing features of human speech such as vowel sound duration, phoneme discrimination, and pause length; all of which involve very precise, small differences in timing. This proposal is specifically interested in the role of inhibition in temporal codes used to process very small differences in spike times. Although it is clear that temporal codes are important for sensory processing, we know relatively little about the cellular mechanisms underlying temporal codes. The relevance of this deficit can be seen in our inability to separate out the many causes of Central Auditory Processing Disorder (CAPD), a group of ill-defined auditory deficiencies resulting from central nervous system dysfunction. The experiments proposed here will take an important step towards elucidating human auditory processing by specifically addressing the role of inhibition in temporal coding. The proposed research will test the hypothesis that inhibition not only generates sensitivity to spike timing differences, but also shapes the representation of that sensitivity by altering how neurons are tuned. Specifically, this research will analyze the role of inhibition at three distinct locations in a neural circuit: the cells providing input to the time-comparator neurons, the time-comparator neurons themselves, and the cells that integrate the outputs of time-comparator neurons. First, a combination of immunohistochemistry and electrophysiology will be used to assess if inhibitory inputs onto inhibitory cells affect sensitivity to spike timing differences. Then, a novel in vivo extracellular axon recording approach will be used along with a pharmacological blocker of inhibition to provide a direct test of how the presence or absence of inhibition affects the tuning properties of time-comparator neurons. Finally, immunohistochemistry and electrophysiology will be used to assess the timing, strength, and location of excitatory and inhibitory inputs onto the neurons that integrate the outputs of time-comparator neurons. All of these experiments will be done using weakly electric fish as a model system because their sensory processing uses small spike timing differences to encode behaviorally relevant signals in an accessible neural circuit devoted exclusively to this sensory modality. The experiments in this proposal will provide critical insight into the diverse roles of inhibition in temporal coding, thus leading to an improved understanding of neural processing of auditory information.

描述（由申请人提供）：该提案的目的是确定控制时间编码中抑制作用的具体机制。时间代码使用精确定时的事件来表示信息。例如，鸟类、哺乳动物和其他脊椎动物的声音定位依赖于时间编码，其中事件是尖峰时间。在这种情况下，神经元首先在相对于声音到达每只耳朵的时间的特定时间发出尖峰。然后，时间比较神经元整合这些尖峰时间，使得特定细胞仅在声音来自特定位置时做出反应。时间编码对于识别人类语音的特征也很重要，例如元音持续时间、音素辨别和停顿长度；所有这些都涉及非常精确、微小的时间差异。该提案特别感兴趣的是用于处理尖峰时间中非常小的差异的时间代码中的抑制作用。尽管时间编码对于感觉处理很重要，但我们对时间编码背后的细胞机制知之甚少。这种缺陷的相关性可以从我们无法区分中枢听觉处理障碍（CAPD）的许多原因中看出，CAPD是一组由中枢神经系统功能障碍引起的不明确的听觉缺陷。这里提出的实验将通过专门解决抑制在时间编码中的作用，向阐明人类听觉处理迈出重要一步。拟议的研究将检验这样的假设：抑制不仅会产生对尖峰时间差异的敏感性，而且还会通过改变神经元的调节方式来塑造这种敏感性的表征。具体来说，这项研究将分析神经回路中三个不同位置的抑制作用：向时间比较器神经元提供输入的细胞、时间比较器神经元本身以及整合时间比较器神经元输出的细胞。首先，免疫组织化学和电生理学的结合将用于评估抑制细胞的抑制输入是否影响对尖峰时间差异的敏感性。然后，一种新颖的体内细胞外轴突记录方法将与抑制药理学阻断剂一起使用，以直接测试抑制的存在或不存在如何影响时间比较器神经元的调谐特性。最后，免疫组织化学和电生理学将用于评估神经元兴奋性和抑制性输入的时间、强度和位置，这些神经元整合了时间比较器神经元的输出。所有这些实验都将使用弱电鱼作为模型系统来完成，因为它们的感觉处理使用小的尖峰时序差异来编码专门用于这种感觉模式的可访问神经电路中的行为相关信号。该提案中的实验将为抑制在时间编码中的不同作用提供重要的见解，从而更好地理解听觉信息的神经处理。

项目成果

Sensory receptor diversity establishes a peripheral population code for stimulus duration at low intensities.

感觉受体多样性为低强度刺激持续时间建立了外围群体代码。

• DOI: 10.1242/jeb.064733
• 发表时间: 2012
• 期刊: The Journal of experimental biology
• 作者: Lyons-Warren,ArielM;Hollmann,Michael;Carlson,BruceA
• 通讯作者: Carlson,BruceA

A diversity of synaptic filters are created by temporal summation of excitation and inhibition.

• DOI: 10.1523/jneurosci.1424-11.2011
• 发表时间: 2011-10-12
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: George AA;Lyons-Warren AM;Ma X;Carlson BA
• 通讯作者: Carlson BA