Actions of proline at receptors and synapses

大脑对氨基酸的处理障碍与多种神经和 行为障碍包括精神分裂症、自闭症、癫痫、智力残疾和抑郁症。虽然 Pro被认为是一种候选的神经递质，证明了Pro能成分 突触功能一直缺乏。脯氨酸被认为在一定程度上通过激活亲离子谷氨酸来调节其作用。 受体，介导中枢神经系统的大部分突触传递。然而，美国政府的行为 谷氨酸受体上的Pro和突触传递还不是很清楚。我们假设 离子型谷氨酸受体对Pro的敏感性随亚单位组成的不同而不同。此外，我们建议 通过药物探测神经元之间的传递可以证明脯氨酸能传递 表达SLC6A7，一种负责大部分突触摄取Pro的高亲和力Pro转运体，以及 它的突触后伙伴。我们将使用电生理，分子，免疫细胞化学， 和成像方法，我们将检查：1)重组亲离子的Pro的药理特性 具有不同亚单位组成的谷氨酸受体；2)作为靶点的首选海马细胞类型 以及3)突触诱发的脯氨酸堆积如何形成谷氨酸能 变速箱。总而言之，这些研究将填补我们对脯氨酸作用的知识的主要空白 在谷氨酸受体和突触上，可能发生了脯氨酸能传递。

Disturbances in brain handling of the amino acid proline are linked to a wide variety neurological and behavioral disorders including schizophrenia, autism, epilepsy, intellectual disability, and depression. Although proline has been suggested to be a candidate neurotransmitter, a demonstration of a prolinergic component of synaptic has been lacking. Proline is thought to mediate its action, in part, via activation of ionotropic glutamate receptors, which mediate the majority of synaptic transmission in the central nervous system. Yet, the actions of proline at glutamate receptors and synaptic transmission are not well understood. We hypothesize that the proline sensitivity of ionotropic glutamate receptors varies with subunit composition. Moreover, we propose that prolinergic transmission can be demonstrated by pharmacologically probing transmission between neurons that express SLC6A7, the high-affinity proline transporter responsible for a majority of synaptic proline uptake, and its postsynaptic partners. We will use a combination of electrophysiological, molecular, immunocytochemical, and imaging methods we will examine: 1) the pharmacological profile of proline at recombinant ionotropic glutamate receptors with distinct subunit compositions; 2) the preferred hippocampal cell types that are targets of putative prolinergic neurons; and 3) the how synaptically evoked proline accumulations shape glutamatergic transmission. Collectively, these studies will fill in major gaps in our knowledge regarding the actions of proline at glutamate receptors and synapses where prolinergic transmission likely occurs.