State dependent dynamics of sensory responses in auditory cortex

描述（由申请人提供）：我们的感知是由我们的行为状态形成的。当我们疲劳时，我们无法注意到通常显著的刺激，当我们专注于一件事时，我们忽略了其他的，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，但大脑中这种“状态依赖”的机制却知之甚少，特别是在神经元和突触的水平上。知觉和行为状态的融合在初级感觉皮层中可能没有更相关，在初级感觉皮层中，感觉知觉和皮层处理首先相遇。因此，了解初级感觉皮层中大脑活动状态依赖的机制是本研究的目标。该项目使用小鼠的听觉系统作为模型，因为听觉对小鼠和人类来说都是一种重要的、发育良好的感觉，也因为它与耳聋、其他交流障碍、精神或神经障碍的理解和潜在治疗相关。

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.