The synaptic basis of cortical taste processing

描述(由申请人提供)：味觉皮质(GC)中的神经元对感觉刺激的反应是其放电频率的时变调制。麻醉和清醒动物的电生理记录表明，放电活动可以在刺激呈现开始后的几秒钟内改变(Grossman等人，2008；Gutierrez等人，2010；Jones等人，2007；Stapleton等人，2006；Yamamoto等人，1984b；Yokota等人，2011)。这些动力学是味觉反应的一个重要特征，并被认为调节味觉信息的不同方面的加工(Fontanini和Katz，2006,2009；Gutierrez等人，2010；Katz等人，2002a)。虽然大量的工作都集中在了解这些模式的功能意义上，但对它们的起源知之甚少。例如，我不知道为什么一些神经元表现出快速的味觉反应，一些神经元在更长的潜伏期(即数百毫秒)被激活，而另一些神经元则根本没有反应。依赖于局部注射GABA阻滞剂荷包牡丹碱的药理学实验表明，抑制是塑造反应的关键因素(Ogawa等人，1998年)。然而，细胞外技术缺乏突触分辨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进程的理解。这一方案中的实验旨在检验时变的尖峰反应由兴奋和抑制的特定组合决定的一般假设。体内细胞内技术的使用将允许在麻醉大鼠中解析突触潜力并剖析兴奋和抑制之间的平衡(Haider等人，2006；Stone等人，2011；Wilent和Contrera，2005)。细胞内注射生物细胞素，然后进行组织重建，将用于鉴定细胞类型和神经元的位置 录制好了。识别记录到的神经元的能力将有助于理解GC不同层和分裂(颗粒状、颗粒状和非颗粒状)的细胞是否显示出特定的突触相互作用模式。对丘脑、杏仁核和味觉刺激的突触反应的分析将使我们能够确定回路中特定的元件如何将自下而上的感觉输入与自上而下的调制相结合。这个框架代表了一种全新的方法来研究完整动物的GC，并有望提供味觉皮质处理的突触基础的第一个综合视图。

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.