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小脑对导水管周围灰质记忆编码及恐惧行为的调节作用

Cerebellar modulation of memory encoding in the periaqueductal grey and fear behaviour.

作者信息

Lawrenson Charlotte, Paci Elena, Pickford Jasmine, Drake Robert A R, Lumb Bridget M, Apps Richard

机构信息

School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom.

出版信息

Elife. 2022 Mar 15;11:e76278. doi: 10.7554/eLife.76278.

Abstract

The pivotal role of the periaqueductal grey (PAG) in fear learning is reinforced by the identification of neurons in male rat ventrolateral PAG (vlPAG) that encode fear memory through signalling the onset and offset of an auditory-conditioned stimulus during presentation of the unreinforced conditioned tone (CS+) during retrieval. Some units only display CS+ onset or offset responses, and the two signals differ in extinction sensitivity, suggesting that they are independent of each other. In addition, understanding cerebellar contributions to survival circuits is advanced by the discovery that (i) reversible inactivation of the medial cerebellar nucleus (MCN) during fear consolidation leads in subsequent retrieval to (a) disruption of the temporal precision of vlPAG offset, but not onset responses to CS+, and (b) an increase in duration of freezing behaviour. And (ii) chemogenetic manipulation of the MCN-vlPAG projection during fear acquisition (a) reduces the occurrence of fear-related ultrasonic vocalisations, and (b) during subsequent retrieval, slows the extinction rate of fear-related freezing. These findings show that the cerebellum is part of the survival network that regulates fear memory processes at multiple timescales and in multiple ways, raising the possibility that dysfunctional interactions in the cerebellar-survival network may underlie fear-related disorders and comorbidities.

摘要

中脑导水管周围灰质(PAG)在恐惧学习中的关键作用因在雄性大鼠腹外侧PAG(vlPAG)中发现神经元而得到加强,这些神经元在检索过程中通过在未强化的条件刺激音(CS+)呈现期间发出听觉条件刺激的开始和结束信号来编码恐惧记忆。一些单元仅显示CS+开始或结束反应,并且这两种信号在消退敏感性方面存在差异,这表明它们彼此独立。此外,通过以下发现,对小脑在生存回路中的作用的理解得到了推进:(i)在恐惧巩固期间内侧小脑核(MCN)的可逆失活导致在随后的检索中,(a)vlPAG结束反应的时间精度受到破坏,但对CS+的开始反应不受影响,以及(b)僵住行为的持续时间增加。并且(ii)在恐惧习得期间对MCN-vlPAG投射进行化学遗传操作,(a)减少了与恐惧相关的超声波发声的发生,以及(b)在随后的检索期间,减缓了与恐惧相关的僵住行为的消退速率。这些发现表明,小脑是生存网络的一部分,该网络在多个时间尺度上并以多种方式调节恐惧记忆过程,这增加了小脑-生存网络中功能失调的相互作用可能是恐惧相关疾病和共病的基础的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad39/8923669/e913c82314f8/elife-76278-fig1.jpg

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