Interactive function of classical neurotransmitters and neuropeptides

神经元的功能不是孤立的，而是作为一个相互连接的网络的一部分。他们可以通过释放GABA和谷氨酸等神经递质直接将信息传递给对方的神经元来做到这一点。此外，神经元还会释放神经肽来调节神经传递。后一个过程虽然对神经元功能至关重要，但很复杂，也没有明确的定义。神经肽与神经递质在同一个神经元中共同表达，但它们由不同的机制释放，并可以通过更长的距离到达它们的靶点。这项建议使用产生黑色素浓缩激素(MCH)的神经元来确定神经递质和神经肽之间的相互作用功能。MCH对正常的能量平衡、奖励和社会行为是必需的，这些行为对生存至关重要，并且在物种之间是保守的。重要的是，MCH神经元形成了研究神经肽网络功能的工具模型，因为它们共同释放神经递质谷氨酸，并且只在大脑的一个区域发现，因此很容易分离出来进行研究。我们最近发现，MCH神经元向外侧隔发出长距离投射，在那里它们释放谷氨酸，并对外侧隔中的细胞进行功能神经支配。在这里，我们将确定是否1)MCH本身也在外侧隔中释放；2)MCH是否调节外侧隔中的谷氨酸能传递；以及3)鉴于谷氨酸在MCH神经元功能中的前所未有的作用，我们将确定MCH和谷氨酸是否具有重叠或独立的行为作用。

Neurons do not function in isolation, but rather, as part of an interconnected network. They can do so by releasing neurotransmitters like GABA and glutamate to directly transmit information to the apposing neuron. Additionally, neurons also release neuropeptides in order to regulate neurotransmission. This latter process though critical to neuronal function, is complex and not well-defined. Neuropeptides co-express with neurotransmitters in the same neuron but they are released by different mechanisms and can travel longer distances to reach their target sites. This proposal uses neurons that produce melanin-concentrating hormone (MCH) to determine the interactive functions between neurotransmitters and neuropeptides. MCH is necessary for normal energy homeostasis, reward and social behaviors, and these actions are critical for survival and are conserved across species. Importantly, MCH neurons form an instrumental model for studying the network functions of a neuropeptide because they co-release the neurotransmitter glutamate and are found only in one region of the brain thus are easily isolated for investigation. We recently showed that MCH neurons send long range projections to the lateral septum where they release glutamate and functionally innervate cells in the lateral septum. Here we will determine if 1) MCH itself is also released in the lateral septum; 2) if MCH regulates glutamatergic transmission in the lateral septum; and 3) given the unprecedented role for glutamate in the function of MCH neurons, we will determine if MCH and glutamate have overlapping or independent behavioral roles.