The synaptic basis of cortical taste processing

描述（由申请人提供）：味觉皮层（GC）中的神经元对感觉刺激的反应是随时间变化的放电率调节。麻醉和清醒动物的电生理记录表明，刺激出现后，放电活动会在几秒钟内发生变化（Grossman等人，2008；Gutierrez等人，2010；Jones等人，2007；Stapleton等人，2006；Yamamoto等人，1984b； Yokota等人，2011）。这些动态是味觉反应的一个关键特征，被认为介导了味觉信息的不同方面的加工（Fontanini和Katz， 2006, 2009； Gutierrez等，2010；Katz等，2002a）。虽然大量的工作集中在理解这些模式的功能意义上，但对它们的起源知之甚少。例如，我们不知道为什么有些神经元表现出快速的味觉反应，有些神经元被激活的潜伏期要长得多（比如几百毫秒），而有些神经元根本没有反应。依赖于局部输注GABA阻滞剂双丘碱的药理学实验表明，抑制作用是形成反应的关键因素（Ogawa等人，1998）。然而，缺乏细胞外技术的突触分辨率限制了我们对抑制和兴奋之间的相互作用如何影响不同神经元反应的时间过程的理解。本实验旨在验证时变尖峰反应是由激发和抑制的特定组合决定的一般假设。使用体内细胞内技术可以解析突触电位并剖析麻醉大鼠的兴奋和抑制之间的平衡（Haider等人，2006；Stone等人，2011；Wilent和Contreras， 2005）。细胞内注射生物细胞素，然后进行组织学重建，将用于识别细胞类型和神经元的位置

DESCRIPTION (provided by applicant): Neurons in the gustatory cortex (GC) respond to sensory stimuli with time-varying modulations of their firing rates. Electrophysiological recordings from anesthetized and awake animals have shown that firing activity can change over few seconds following the onset of stimulus presentation (Grossman et al., 2008; Gutierrez et al., 2010; Jones et al., 2007; Stapleton et al., 2006; Yamamoto et al., 1984b; Yokota et al., 2011). These dynamics are a critical feature of gustatory responses and are believed to mediate the processing of different aspects of gustatory information (Fontanini and Katz, 2006, 2009; Gutierrez et al., 2010; Katz et al., 2002a). While a great deal of work has focused on understanding the functional significance of these patterns, little is known about their genesis. I is not known, for instance, why some neurons display rapid taste responses, some are activated at much longer latencies (i.e. hundreds of milliseconds) and some others do not respond at all. Pharmacological experiments relying on local infusions of the GABA blocker bicuculline point to inhibition as a key player in shaping responses (Ogawa et al., 1998). However, the lack of synaptic resolution of extracellular techniques has limited our understanding of how interactions between inhibition and excitation could influence the time course of responses in different neurons. The experiments in this proposal are designed to test the general hypothesis that time-varying spiking responses are determined by specific combinations of excitation and inhibition. The use of in vivo intracellular techniques will allow to resolve synaptic potentials ad dissect the balance between excitation and inhibition in anesthetized rats (Haider et al., 2006; Stone et al., 2011; Wilent and Contreras, 2005). Intracellular injection of biocytin, followed by histological reconstructions, will be used to identify the cell type and the location of the neuron recorded. The ability to identify the recorded neurons will be instrumental in understanding whether cells in the different layers and divisions (granular, dysgranular and agranular) of GC show specific patterns of synaptic interactions. The analysis of synaptic responses to thalamic, amygdalar and gustatory stimulation will allow us to determine how specific elements in the circuit integrate bottom-up sensory inputs with top-down modulations This framework represents an entirely novel approach to the study of GC in intact animals and promises to provide the first integrative view of the synaptic bases of gustatory cortical processing.