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表达钙结合蛋白的基底前脑神经元介导了从负面经验中学习。

Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience.

机构信息

Lendület Laboratory of Systems Neuroscience, HUN-REN Institute of Experimental Medicine, H-1083, Budapest, Hungary.

János Szentágothai Doctoral School of Neurosciences, Semmelweis University, H-1085, Budapest, Hungary.

出版信息

Nat Commun. 2024 Jun 7;15(1):4768. doi: 10.1038/s41467-024-48755-7.

DOI:10.1038/s41467-024-48755-7
PMID:38849336
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11161511/
Abstract

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system, yet their exact role in awake behaviors remains unclear. We performed bulk calcium measurements and electrophysiology with optogenetic tagging from the horizontal limb of the diagonal band of Broca (HDB) while male mice were performing an associative learning task. BFPVNs responded with a distinctive, phasic activation to punishment, but showed slower and delayed responses to reward and outcome-predicting stimuli. Optogenetic inhibition during punishment impaired the formation of cue-outcome associations, suggesting a causal role of BFPVNs in associative learning. BFPVNs received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key limbic structures, where they broadcasted information about aversive stimuli. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions.

摘要

基底前脑表达钙结合蛋白 Parvalbumin(PV)的 GABA 能神经元(BFPVNs)被认为是一种快速而短暂的觉醒系统,但它们在清醒行为中的确切作用仍不清楚。我们在雄性小鼠执行联想学习任务时,通过 Broca 水平束(HDB)的水平支进行了钙含量的批量测量和光遗传学标记。BFPVNs 对惩罚有独特的、阶段性的激活反应,但对奖励和结果预测性刺激的反应较慢且延迟。在惩罚期间进行光遗传学抑制会损害线索-结果关联的形成,这表明 BFPVNs 在联想学习中起因果作用。BFPVNs 从下丘脑、隔核复合体和中缝脑区接收到强烈的输入,同时它们与关键边缘结构中的多种细胞类型形成突触,在这些结构中传播关于厌恶刺激的信息。我们提出,BFPVNs 的唤醒效应被厌恶刺激募集,以服务于关键的联想学习功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/974d921676b4/41467_2024_48755_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/6fee854b949e/41467_2024_48755_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/f5a4fd71963b/41467_2024_48755_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/5bcc3aa39459/41467_2024_48755_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/ccd09b902774/41467_2024_48755_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/6d13f285190e/41467_2024_48755_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/c8f8aca99c6f/41467_2024_48755_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/259e6cfc8a7a/41467_2024_48755_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/974d921676b4/41467_2024_48755_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/6fee854b949e/41467_2024_48755_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/f5a4fd71963b/41467_2024_48755_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/5bcc3aa39459/41467_2024_48755_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/ccd09b902774/41467_2024_48755_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/6d13f285190e/41467_2024_48755_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/c8f8aca99c6f/41467_2024_48755_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/259e6cfc8a7a/41467_2024_48755_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b45/11161511/974d921676b4/41467_2024_48755_Fig8_HTML.jpg

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