The Role of Glutamate and CCK in the PBN in Taste Reactivity

描述(申请人提供)：这项研究的长期目标是阐明大鼠味觉输入引发的进食相关行为的中枢神经机制。最近的研究集中在两个接受味觉信息的脑干区域，孤束嘴核和臂旁核(PBN)。PBN在处理感觉信息和启动口腔运动反应中的作用特别耐人寻味，因为PBN中的神经元处理与味道相关的感觉信息，并投射到延髓中控制口腔运动行为的运动神经元网络。将谷氨酸直接注射到清醒大鼠的PBN味觉区域，引起嘴巴运动和舌头伸出等进食行为，这表明PBN内的谷氨酸能神经传递在启动口腔运动行为中发挥了作用。因此，这项研究的第一个具体目标是确定PBN中的谷氨酸受体在味觉刺激引起的运动行为中的作用。据推测，谷氨酸受体的激活是正常行为反应所必需的。CCK是一种具有饱腹感的肠肽。有一些证据表明CCK调节摄食行为，但CCK及其受体在PBN中的特定功能作用尚未得到解决。因此，这项研究的第二个具体目的是确定PBN中CCK在口腔内滴注味觉溶液引起的清醒大鼠口腔运动行为中的作用。假设是，与其在饱腹感中的作用一致，CCK将减少对味觉输入的消化或运动反应。这两个特定的目标将通过在PBN和口腔内植入插管来实现，以便在清醒大鼠将味觉溶液注入口腔之前，立即将谷氨酸或CCK受体阻滞剂注入PBN。这项拟议的研究与公共健康相关，因为它将提高对脑干内控制味觉输入行为反应的神经回路的理解。这些行为反应对生存至关重要，因为它们导致对适当食物的接受和对潜在毒素的排斥。具体地说，在拟议的调查期间收集的数据将确定PBN中的谷氨酸和CCK是否在评估摄取的物质和随后的行为反应中发挥关键作用。

DESCRIPTION (provided by applicant): The long-term goal of this research is to elucidate the central neural mechanisms underlying feeding-related behaviors initiated by taste input in the rat. Recent studies have focused on the neurochemistry of two brainstem areas that receive gustatory sensory information, the rostral nucleus of the solitary tract and the parabrachial nucleus (PBN). The role of the PBN in the processing of sensory information and the initiation of oromotor responses is particularly intriguing since neurons in the PBN process taste-related sensory information and project to the network of motor neurons in the medulla that controls oromotor behaviors. Suggesting a role for glutamatergic neurotransmission within the PBN in the initiation of oromotor behaviors, microinjection of glutamate directly into the taste regions of the PBN in conscious rats elicits ingestive behaviors like mouth movements and tongue protrusions. Therefore, the first specific aim of the proposed study is to determine the role of glutamate receptors within the PBN in oromotor behaviors elicited by taste stimulation. It is hypothesized that the activitation of glutamate receptors is necessary for normal behavioral responses. Cholecystokinin (CCK) is a gut peptide that has satiety effects. There is some evidence that CCK modulates ingestive behaviors but a specific functional role for CCK and its receptors within the PBN has not been addressed. Therefore, the second specific aim of the proposed study is to determine the role of CCK in the PBN in oromotor behaviors elicited by intra-oral infusion of taste solutions in conscious rats. The hypothesis is that, consistent with its role in satiety, CCK will reduce ingestive oromotor responses to taste input. Both specific aims will be addressed by implanting cannula into the PBN as well as into the oral cavity so that glutamate or CCK receptor blockers can be injected into the PBN immediately prior to infusing taste solutions into the oral cavity in conscious rats. The proposed research is relevant to public health because it will improve the understanding of the neural circuits within the brainstem that control behavioral responses to taste input. These behavioral responses are critical to survival since they result in the acceptance of appropriate foods and rejection of potential toxins. Specifically, data collected during the proposed investigation will determine if glutamate and CCK in the PBN play a critical role in the assessment of ingested substances and subsequent behavioral responses.