Sensory Coding in Taste

描述（由申请人提供）：味觉系统提供关于食物摄入的决定所必需的感觉信息，其通过其对肥胖、糖尿病、心脏病、高血压和中风等病症的影响而在人类健康中起关键作用。关于中枢味觉反应神经元在编码刺激质量与适口性中所起的不同作用知之甚少，这最终指导了摄入。这里提出的研究测试的假设，即在臂旁核（PbN），投射到丘脑腹后内侧核（VPMpc）的神经元编码的味道质量更重要，而那些投射到边缘前脑，特别是中央核杏仁核（CeA）的神经元，编码的适口性是至关重要的。三个具体的目标解决的假设，味觉反应神经元包括平行的功能通路。目的1：研究丘脑和杏仁核PbN神经元的味觉反应特性。这些研究使用细胞外记录来检查PbN神经元如何对质量和适口性不同的刺激（蔗糖、NaCl、HCl和盐酸奎宁的浓度系列）作出反应;使用植入这些靶核中的电极的逆向激活在体内鉴定投射到VPMpc和CeA的神经元。由于适口性，但不是质量，改变后条件性味觉厌恶（CTA），VPMpc和CeA投射神经元的反应进行检查后，厌恶0.5 M蔗糖，这应该改变CeA投射细胞的反应。目的2：研究味觉激活的Fos蛋白在丘脑或杏仁核PbN神经元中的分布。这些研究检查了由不同口味质量和适口性的刺激激活的神经元的分布，并使用CTA蔗糖来改变适口性，并确定投射到CeA的细胞在此操作后是否被差异激活。目的3：研究丘脑或杏仁核投射的PbN神经元的特性。这些研究采用膜片钳记录从PbN中的神经元，其在记录之前已经用荧光示踪剂逆行标记，以将它们识别为投射到VPMpc或CeA，结合生物胞素填充以检查神经元形态。这些实验检验了以下假设：投射到VPMpc和CeA的神经元之间存在电压激活电导和细胞形态的差异。

DESCRIPTION (provided by applicant): The gustatory system provides sensory information that is necessary for decisions about food intake, which plays a critical role in human health through its impact on such conditions as obesity, diabetes, heart disease, hypertension, and stroke. Little is known about the differential roles played by central taste- responsive neurons in coding stimulus quality vs. palatability, which ultimately guides ingestion. The studies proposed here test the hypothesis that neurons in the parabrachial nuclei (PbN) that project to the ventral posterior medial nucleus of the thalamus (VPMpc) are more important for coding taste quality, whereas those neurons projecting to the limbic forebrain, specifically to the central nucleus of the amygdala (CeA), are critical for coding palatability. Three specific aims address the hypothesis that taste-responsive neurons comprise parallel functional pathways. Aim 1: To determine the gustatory response properties of PbN neurons projecting to the thalamus or amygdala. These studies use extracellular recording to examine how PbN neurons respond to stimuli that vary in quality and palatability (concentration series of sucrose, NaCI, HCI and quinine hydrochloride); neurons projecting to the VPMpc and the CeA are identified in vivo using antidromic activation from electrodes implanted in these target nuclei. Since palatability, but not quality, is altered following conditioned taste aversion (CTA), the responses of VPMpc- and CeA-projecting neurons are examined following an aversion to 0.5 M sucrose, which should alter responses in CeA-projecting cells. Aim 2: To determine the distribution of gustatory-activated Fos expression in PbN neurons retrogradely labeled from the thalamus or amygdala. These studies examine the distribution of neurons activated by stimuli differing in taste quality and palatability and use CTA to sucrose to alter palatability and determine whether cells projecting to the CeA are differentially activated after this manipulation. Aim 3: To determine the intrinsic properties of PbN neurons projecting to the thalamus or amygdala. These studies employ patch-clamp recording from neurons in the PbN that have been retrogradely labeled with fluorescent tracers prior to recording to identify them as projecting to the VPMpc or the CeA, combined with biocytin fills to examine neuronal morphology. These experiments test the hypothesis that there are differences in voltage- activated conductances and cell morphology between neurons projecting to the VPMpc and the CeA.