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

描述（由申请人提供）：本研究的长期目标是阐明大鼠中由味觉输入引发的摄食相关行为的中枢神经机制。最近的研究集中在两个脑干区域，接受味觉感觉信息，孤束吻侧核和臂旁核（PBN）的神经化学。PBN在感觉信息的处理和orthopathic反应的启动中的作用是特别有趣的，因为PBN中的神经元处理与味觉相关的感觉信息，并投射到控制orthopathic行为的延髓中的运动神经元网络。提示PBN内的谷氨酸能神经传递在启动食欲行为中的作用，将谷氨酸直接微量注射到清醒大鼠PBN的味觉区中，可诱发摄食行为，如嘴部运动和舌头伸出。因此，本研究的第一个具体目的是确定PBN内谷氨酸受体在味觉刺激引起的嗅觉行为中的作用。据推测，谷氨酸受体的激活是正常行为反应所必需的。胆囊收缩素（CCK）是一种具有饱腹感作用的肠道肽。有一些证据表明CCK调节摄食行为，但CCK及其受体在PBN内的特定功能作用尚未得到解决。因此，建议的研究的第二个具体目标是确定CCK在PBN中的作用，在清醒大鼠口腔内输注味觉溶液引起的orrhagic行为。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摄食或消化反应。这两个具体目标将通过将套管植入PBN以及口腔中来解决，使得谷氨酸或CCK受体阻断剂可以在将味觉溶液注入清醒大鼠的口腔中之前立即注入PBN中。这项拟议中的研究与公共卫生有关，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，因为它们导致接受适当的食物和拒绝潜在的毒素。具体而言，在拟议的研究期间收集的数据将确定PBN中的谷氨酸盐和CCK是否在评估摄入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.