The role of excitatory VTA projections in novelty-dependent behavior

兴奋性 VTA 投射在新奇依赖行为中的作用

基本信息

批准号：
10720976
负责人：
Olalekan Michael Ogundele
金额：
$ 36.53万
依托单位：
LOUISIANA STATE UNIV A&M COL BATON ROUGE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10720976
关键词：
Adaptive Behaviors Anatomy Architecture Area Behavior Bipolar Depression Brain Brain region Cell Nucleus Cells Cognitive Dendrites Desire for food Detection Discrimination Disease Dopamine Electrophysiology (science)Extinction Food Frequencies Future Glutamates Goals Hallucinations Hippocampus Interneurons Knowledge Learning Link Medial Memory Mental Depression Methods Midbrain structure Mus Nature Neurons Neurotransmitters Noise Pathway interactions Pattern Physiological Positive Valence Prefrontal Cortex Pyramidal Cells Research Rewards Role Schizophrenia Stimulus System Ventral Tegmental Area addiction autism spectrum disorder behavioral phenotyping cognitive control cognitive process dopaminergic neuron experimental study gamma-Aminobutyric Acid habituation in vivo learned behavior neural neural circuit neuropsychiatric disorder novel optogenetics social social contact

项目摘要

PROJECT SUMMARY Learning and memory involve multiple brain areas. However, the hippocampus (CA1) and ventral tegmental area (VTA) are the brain regions primarily involved in novelty detection and context discrimination. Abnormal connection between these brain regions leads to deficits in novelty behavior. For decades, the function of the VTA-CA1 circuit in learning, and the dysregulation of midbrain neurotransmitter systems in diseases like schizophrenia, depression, and addictions have been attributed (primarily) to the dopamine neurons. Because of this traditional focus on the midbrain dopaminergic systems, the glutamate pathway has been overlooked and is less understood in normal brain function and neuropsychiatric disorders. In a recent study, we showed that the VTA glutamate terminals are anatomically dominant in the CA1 while VTA dopamine terminals were limited to the basal dendrite layer. Functional tracing of the VTA-CA1 pathway shows that selective activation of VTA glutamate and dopamine neurons has distinguishable effects on CA1 local circuits. Photostimulation of VTA glutamate – but not the dopamine – neurons increased burst firing of CA1 pyramidal cells. Likewise, stimulation of the VTA glutamate pathway increased putative pyramidal cells (PYR) excitation of interneurons (INT) in CA1 ensembles. In freely behaving mice, novelty detection tasks that activate the VTA-CA1 circuit increased CA1 PYR/INT connectivity while its inhibition altered novelty-linked behavior. Based on preliminary results, the proposed research will elucidate the functional significance of the VTA glut→CA1 tract in the hippocampal encoding of novelty-dependent behavior including context discrimination and habituation. The results of the proposed research will increase our understanding of VTA excitatory modulation of cognitive processes and control of adaptive behavior.

项目概要学习和记忆涉及多个大脑区域，但其中包括海马体（CA1）和腹侧被盖区。（VTA）是主要参与新颖性检测和异常情境辨别的大脑区域。几十年来，这些大脑区域之间的联系导致了新奇行为的缺陷。学习中的 VTA-CA1 回路，以及中脑神经递质系统在疾病中的失调精神分裂症、抑郁症和成瘾症（主要）归因于多巴胺神经元。这种对中脑多巴胺能系统的传统关注，谷氨酸途径被忽视了在最近的一项研究中，我们对正常大脑功能和神经精神疾病的了解较少。 VTA 谷氨酸末端在 CA1 中占解剖学主导地位，而 VTA 多巴胺末端则有限 VTA-CA1 通路的功能追踪表明 VTA 的选择性激活。谷氨酸和多巴胺神经元对 VTA 的 CA1 局部回路有明显的影响。谷氨酸（但不是多巴胺）神经元会增加 CA1 锥体细胞的爆发放电，同样，刺激也会增加。 VTA 谷氨酸途径的增加增加了 CA1 中假定的锥体细胞 (PYR) 中间神经元 (INT) 的兴奋在自由行为的小鼠中，激活 VTA-CA1 回路的新奇检测任务增加了 CA1。 PYR/INT 连接性同时其抑制改变了新颖性相关行为。拟议的研究将阐明海马中 VTA glut→CA1 束的功能意义编码依赖新奇的行为，包括情境歧视和习惯化。拟议的研究将增加我们对认知过程的 VTA 兴奋性调节的理解适应性行为的控制。