Function of thalamic excitatory synapses in social reward processing

 描述(由申请人提供)：迅速变得清楚的是，精神障碍的症状，如社交回避，在多种情况下存在，可能具有单一的神经功能障碍。社会异常存在于自闭症、精神分裂症、抑郁症和与焦虑相关的障碍中，占患有精神疾病的人口的很大一部分。虽然存在许多药物疗法，但治疗大多数患者的成功率令人惊讶地低。这突显了研究多个模型中常见症状的紧迫性，同时检查新的大脑回路，以解析导致适应不良行为的特定适应。虽然大脑的多巴胺系统显然与精神障碍有关，但大脑的主要神经递质谷氨酸也 最近与潜在的某些精神症状有关，但由于它在大脑中无处不在，其功能一直难以确定。许多关于压力对大脑影响的研究都发现，压力会改变细胞的形态和电学特性，然而，这些研究中的许多都发生在离散的大脑区域，而不知道细胞的输入。随着新的病毒技术和转基因小鼠品系的出现，现在有可能分离特定的突触，细胞之间的通信点，以发现哪些谷氨酸能途径参与特定的行为。在这项建议中，我将利用两种压力范式(社会性和非社会性)来分离社会压力对社会奖励的影响 正在处理。我将利用利用光激活离子通道和转基因细胞系的特定细胞的操纵，结合电生理学来研究丘脑的谷氨酸能突触，这些突触影响到在奖赏处理和社会行为中重要的区域，特别是前额叶皮质和伏隔核。这一建议假设，与非社会压力相比，社会压力将具有独特的突触适应，这些适应具体涉及到调节社会回报的处理。初步结果表明，丘脑细胞突触伏核神经元参与了社会互动，并因社会应激选择性地损害了社会条件性位置偏爱的获得。这项研究将寻求进一步了解改变这些突触的活动如何减轻应激诱导的社会行为损害，以及检查其他可能调节社会行为的丘脑回路。从这些研究中收集的信息将为开发独特的治疗方法提供新的起点，以改变电路功能并缓解精神障碍的特定症状。

 DESCRIPTION (provided by applicant): It is fast becoming clear that symptoms of psychiatric disorders, such as social avoidance, which are present in multiple conditions, may have singular neural dysfunctions underlying their presentation. Social abnormalities are present in autism, schizophrenia, depression and anxiety-related disorders, representing a significant portion of the population afflicted with mental disease. While many pharmacotherapies exist, the success rate of treating a majority of patients is surprisingly low. This highlights the urgency in studyin common symptoms across multiple models, while examining new brain circuits to parse out specific adaptations responsible for maladaptive behaviors. While the brain's dopamine system is clearly involved in psychiatric disorders, the brain's major neurotransmitter glutamate has also recently been implicated in underlying certain psychiatric symptoms, yet due to its ubiquity throughout the brain, its function has been difficult to determine. Many studies of the effects of stress on the brain have seen that it alters cell morphology and electrical properties, however many of these studies have occurred in discrete brain regions without knowledge of the input to the cell. With the advent of novel viral techniques and transgenic mouse lines it is now possible to isolate specific synapses, the point of communication between cells, to discover which glutamatergic pathways are involved in a specific behavior. In this proposal I will utilize two stress paradigms (a social and non-social) to isolate the effects of social stress on social reward processing. I will utilize manipulation of specific cells with light-activated ion channels and transgenic lines in combination with electrophysiology to study glutamatergic synapses of the thalamus impinging upon regions important in reward processing and social behavior, specifically the prefrontal cortex and nucleus accumbens. This proposal hypothesizes that social stress will have unique synaptic adaptations when compared to non-social stress and these adaptions are specifically involved in regulating social reward processing. Preliminary results demonstrate the involvement of thalamic cells synapsing on nucleus accumbens neurons in social interaction and the impaired acquisition of a social conditioned-place preference selectively by social stress. This study will seek to further understand how altering activity at these synapses can alleviate stress induced impairments in social behavior, as well as examining other thalamic based circuits that may regulate social behavior. The information gathered from these studies will provide novel starting points for developing unique therapies to alter circuit function and alleviate specific symptoms of psychiatric disorders.