Sensory Coding in Taste

描述（由申请人提供）：味觉系统提供关于食物摄入决策所必需的感觉信息，它通过影响肥胖、糖尿病、心脏病、高血压和中风等疾病，在人类健康中起着至关重要的作用。关于中枢味觉反应神经元在编码刺激质量和适口性方面所起的不同作用，我们所知甚少，最终指导摄入。本文提出的研究验证了一个假设，即投射到丘脑腹侧后内侧核（VPMpc）的臂旁核（PbN）神经元对编码味觉质量更重要，而投射到边缘前脑，特别是杏仁核中央核（CeA）的神经元对编码适口性至关重要。三个特定的目标解决了味觉反应神经元包含平行功能通路的假设。目的1：确定投射到丘脑或杏仁核的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宜性不同的刺激（蔗糖、NaCI、HCI和盐酸奎宁的浓度系列）作出反应；投射到VPMpc和CeA的神经元在体内通过植入这些靶核的电极的反激激活来识别。由于适口性，而不是质量，在条件性味觉厌恶（CTA）之后被改变，VPMpc-和cea -投射神经元的反应在厌恶0.5 M蔗糖后被检查，这应该改变cea -投射细胞的反应。目的2：确定味觉激活的Fos在丘脑或杏仁核逆行标记的PbN神经元中的表达分布。这些研究检查了不同味觉质量和适口性刺激激活的神经元分布，并使用CTA和蔗糖来改变适口性，并确定在这种操作后，投射到CeA的细胞是否被不同的激活。目的3：确定投射到丘脑或杏仁核的PbN神经元的内在特性。这些研究采用膜片钳对PbN中的神经元进行记录，这些神经元在记录之前已经用荧光示踪剂逆行标记，以确定它们是投射到VPMpc或CeA上，并结合生物细胞素填充来检查神经元形态。这些实验验证了在投射到VPMpc和CeA的神经元之间存在电压激活电导和细胞形态差异的假设。

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.