A highly opioid responsive VTA projection to the dorsal endopiriform nucleus.

高度阿片类药物反应的 VTA 投射到背内核状核。

基本信息

批准号：
10739039
负责人：
Elyssa Margolis
金额：
$ 24.23万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
2023-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739039
关键词：
Acceleration Agonist Alcohol consumption Anatomy Animals Attention Behavior Brain Brain region Cell Nucleus Cerebral cortex Claustral structure Conscious Cues Development Disease Dopamine Dorsal G-Protein-Coupled Receptors Generations Genetic Health Investigation Label Learning Light Link Maps Medial Messenger RNA Modality Motivation Neurons Neurotransmitters Nucleus Accumbens Opioid Opioid Peptide Opioid Receptor Optics Outcome Output Performance Phenotype Play Prefrontal Cortex Prosencephalon Proteins Psychological reinforcement Receptor Activation Resolution Rewards Role Seizures Sensory Signal Transduction Site Stress Structure Synapses Techniques Testing Thinness Time Tracer Ventral Tegmental Area Viral Vector Whole-Cell Recordings delta opioid receptor design endogenous opioids experimental study food consumption kappa opioid receptors motivated behavior mu opioid receptors nerve supply neural neurochemistry neurotransmitter release postsynaptic preference receptor expression receptor function response sensory cortex sensory input sensory integration tool

项目摘要

SUMMARY The dorsal endopiriform nucleus (DEn) is a highly conserved structure found in mammalian brains that is developmentally related to the claustrum and has been linked to the claustrum's role as the “seat of consciousness”. The DEn is connected to more limbic regions than the claustrum, has a very dense projection to infralimbic cortex, and receives strong inputs from sensory cortices especially olfactory and gustatory regions. While the DEn's role in behavior remains largely unknown beyond contributing to the generation of seizure activity, it has long been known to have extremely high levels of mu, delta, and kappa opioid receptor (MOR, DOR, and KOR) protein and mRNA. In preliminary studies we discovered a mostly non-dopaminergic ventral tegmental area (VTA) projection to the DEn; these neurons show a significantly stronger hyperpolarization in response to the MOR agonist DAMGO than any other VTA projection we have investigated. This is an exciting find because opioid reward, including intra-VTA opioid reward, is dopamine independent in opioid naïve animals. Thus, this non-dopaminergic, MOR sensitive projection may contribute to this opioid reward. Since the DEn receives inputs from a variety of sensory cortices, this is also a potential site of direct interaction between reinforcement encoding from the VTA and sensory cue information. Here we propose to anatomically map the VTA innervation of the DEn, characterize the VTA  DEn synaptic connectivity including its MOR sensitivity, and test whether selective modulation of this circuit connection produces reward or promotes learning or salience signaling. Together these studies will lay the groundwork for understanding a previously unstudied but highly opioid sensitive output of the VTA to an opioid receptor enriched brain region situated to integrate information from across cerebral cortex.

概括背尿内一核（DEN）是在哺乳动物大脑中发现的高度组成结构与claustrum相关的开发，并与Claustrum的角色联系在一起意识”。巢穴与隔离区更具边缘区域相关，具有非常密集的投影输入皮层，并从感觉皮质中收到强大的输入，尤其是嗅觉和味道区域。虽然丹在行为中的作用仍然是未知的，但有助于发作的产生活性，长期以来，它具有极高的MU，三角洲和Kappa阿片类药物受体（MOR，MOR， dor和kor）蛋白质和mRNA。在初步研究中，我们发现了大多数非胃激素能腹对DEN的段落区域（VTA）投影；这些神经元在对MOR激动剂Damgo的反应比我们研究的任何其他VTA投影。这是一个令人兴奋的找到是因为阿片类药物奖励（包括VTA阿片类药物奖励）在阿片类幼稚动物中独立于多巴胺。这是这种非胃激素能敏感投影可能有助于这种阿片类药物的奖励。自从书房以来从各种感觉皮层接收输入，这也是一个潜在的直接相互作用的站点从VTA和感觉提示信息编码的加固。在这里，我们建议在解剖学上映射 DEN的VTA神经支配，表征VTADEN突触连接性，包括其MOR敏感性，并测试该电路连接的选择性调制是否产生奖励或促进学习或显着性信号。这些研究共同为理解以前未研究但高度的基础是基础 VTA对蛋白质接收器的蛋白敏感输出富含脑部的脑区域，该区域位于集成信息从跨大脑皮层。