Sensory Coding in Taste

描述(由申请人提供)：味觉系统提供决定食物摄入量所需的感觉信息，通过影响肥胖、糖尿病、心脏病、高血压和中风等疾病，对人类健康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与适口性方面所扮演的不同角色，人们知之甚少，后者最终指导着摄取。这里提出的研究验证了一种假设，即投射到丘脑腹侧后内侧核(VPMpc)的臂旁核(PBN)中的神经元对编码味觉质量更重要，而那些投射到边缘前脑，特别是杏仁中央核(CEA)的神经元对编码味觉至关重要。三个特定的目标解决了味觉反应神经元由平行的功能通路组成的假设。目的1：测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测PBN神经元对质量和适口性不同的刺激(蔗糖、NaCI、盐酸和奎宁的浓度系列)的反应；投射到VPMPC和CEA的神经元在体内使用植入这些靶核的电极的反向激活来识别。由于在条件性味觉厌恶(CTA)后，适口性而不是品质发生了改变，因此我们研究了VPMpc和CEA投射神经元在厌恶0.5M蔗糖后的反应，这应该会改变CEA投射细胞的反应。目的：确定味觉激活的Fos在丘脑或杏仁核逆行标记的PBN神经元中的分布。这些研究检测了不同味道质量和适口性刺激激活的神经元的分布，并使用CTA对蔗糖改变适口性，并确定投射到CEA的细胞在这种操作后是否有不同的激活。目的3：确定向丘脑或杏仁核投射的PBN神经元的固有特性。这些研究使用膜片钳记录PBN中的神经元，这些神经元在记录之前被逆行标记荧光示踪剂，以识别它们投射到VPMPC或CEA，结合生物细胞素填充来检查神经元的形态。这些实验验证了投射到VPMPC和CEA的神经元在电压激活电导和细胞形态上存在差异的假设。

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.