State dependent dynamics of sensory responses in auditory cortex

听觉皮层感觉反应的状态依赖动力学

• 批准号: 8453599
• 负责人: Matthew J McGinley
• 金额: $ 5.22万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453599
• 关键词: Affect; Anesthesia procedures; Animal Behavior; Animals; Area; Attention; Auditory; Auditory area; Auditory system; Automobile Driving; Behavior monitoring; Behavioral; Brain; Brain Diseases; Cells; Communication impairment; Complex; Custom; Data; Dependence; Depressed mood; Equilibrium; Foundations; Fourier Transform; Future; Goals; Head; Hearing; Human; Interneurons; Label; Location; Locomotion; Mammals; Measures; Membrane Potentials; Mental disorders; Methods; Microscope; Mind; Modeling; Monitor; Motivation; Movement; Mus; Neurons; Perception; Physiology; Play; Population; Preparation; Process; Prosencephalon; Proxy; Research; Role; Sensory; Sensory Process; Shapes; Sleep; Somatosensory Cortex; Stimulus; Stream; Structure; Synapses; Techniques; Time; Visual; Visual Cortex; Wakefulness; Walking; Work; alertness; awake; base; blind; deafness; design; experience; extracellular; hippocampal pyramidal neuron; improved; inhibitory neuron; insight; meetings; nervous system disorder; neural circuit; patch clamp; phrases; postsynaptic; receptive field; research study; response; sensory cortex; sensory stimulus; sound; two-photon; voltage clamp

DESCRIPTION (provided by applicant): Our perception is shaped by our behavioral state. When we are tired we fail to notice normally salient stimuli, when focused on one thing we ignore others, and with practice we can even improve our ability to perceive. While these are basic aspects of experience, the mechanisms in the brain of such 'state dependence' are poorly understood, particularly at the level of neurons and synapses. The convergence of perception and behavioral state is perhaps no more relevant than in primary sensory cortex, where sensory perception and cortical processing first meet. Therefore, it is the goal of this proposal to understand the mechanisms of the state dependence of brain activity in primary sensory cortex. This project uses the auditory system of mice as a model, because hearing is an important, well developed sense for both mice and humans, and because of the relevance for the understanding and potential treatment of deafness, other communication disorders, and psychiatric or neurologic disorders. To 'zoom in' to the cellular and synaptic level in a perceiving and behaving animal this study uses a powerful set of cutting edge techniques: two-photon targeted and blind patch- clamp recording along with custom-developed behavioral and sensory stimulus delivery methods. This integrative approach will hopefully allow us to answer a basic important question about the state dependence of perception. How do the circuit dynamics in auditory cortex change when an animal is alert or mobile when compared to passively sitting still? In particular, we will determine how principal neuron firing is regulated by inhibitory and excitatory synaptic activity, and what types of inhibitory neurons appears to be responsible for the inhibitory component. To do so, we will monitor the movements of the animal on a custom designed treadmill apparatus, and measure alertness by recording the local field potential (LFP) and multiunit firing in multiple forebrain areas. These experiments will provide new insights into the dynamics of cortical sensory responses as they relate to the state of the animal. This work will also provide a foundation of methods and results for future study of how the modulation of perception by behavioral state is perturbed in deafness and brain diseases. PUBLIC HEALTH RELEVANCE: The popular phrase 'mind over matter' expresses the fact that our perception is shaped by our internal state of being, such as: sleepy or alert, or pathological states like hallucinating or depressed. Such 'state dependence' is a complex yet very important facet of our experience and therefore elucidating its brain manifestations has broad implications for understanding the healthy brain and psychiatric illness. This research proposes to explore how the basic cellular and synaptic physiology in auditory cortex, measured in responses to sounds, is altered in mice between different states of wakefulness and locomotion.

描述(申请人提供)：我们的感知是由我们的行为状态决定的。当我们疲倦时，我们无法注意到通常显著的刺激，当我们专注于一件事情时，我们忽略了其他事情，通过练习，我们甚至可以提高我们的感知能力。虽然这些都是经验的基本方面，但人们对这种“状态依赖”的大脑机制知之甚少，特别是在神经元和突触的水平上。知觉和行为状态的融合可能并不比初级感觉皮层更相关，初级感觉皮层是感觉知觉和皮质处理最先相遇的地方。因此，了解初级感觉皮层脑活动的状态依赖性机制是本研究的目的。这个项目使用小鼠的听觉系统作为模型，因为听力对小鼠和人类都是一种重要的、发育良好的感觉，也因为它与耳聋、其他沟通障碍以及精神或神经障碍的理解和潜在治疗有关。 为了“放大”感知和行为动物的细胞和突触水平，这项研究使用了一套强大的尖端技术：双光子靶向和盲膜片钳记录，以及定制开发的行为和感觉刺激传递方法。这种综合的方法有望让我们回答一个关于知觉的国家依赖性的基本重要问题。当动物处于警觉或活动状态时，与被动静坐相比，听觉皮质中的电路动力学是如何变化的？特别是，我们将确定主神经元放电是如何受到抑制性和兴奋性突触活动的调节的，以及哪些类型的抑制性神经元似乎对抑制性成分负责。为此，我们将在定制设计的跑步机设备上监测动物的运动，并通过记录多个前脑区域的局部场电位(LFP)和多单位放电来测量警觉性。 这些实验将为皮质感觉反应的动力学提供新的见解，因为它们与动物的状态有关。这项工作也将为进一步研究行为状态对知觉的调节如何在耳聋和脑疾病中起到干扰作用提供方法和结果的基础。 与公共健康相关：流行的短语“思想重于物质”表达了这样一个事实，即我们的感知是由我们的内在状态塑造的，比如：昏昏欲睡或警觉，或者像幻觉或抑郁这样的病理状态。这种‘状态依赖’是我们经验中一个复杂而又非常重要的方面，因此，阐明其大脑表现对于理解健康的大脑和精神疾病具有广泛的意义。这项研究建议探索在不同的清醒和运动状态下，小鼠听觉皮质的基本细胞和突触生理学是如何改变的，这是通过对声音的反应来衡量的。