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猕猴背外侧膝状核膝状皮质神经元中GABAA受体亚基的选择性表达与快速调节

Selective expression and rapid regulation of GABAA receptor subunits in geniculocortical neurons of macaque dorsal lateral geniculate nucleus.

作者信息

Hendry S H, Miller K L

机构信息

Zanvyl Krieger Mind/Brain Institute, Department of Neuroscience, Johns Hopkins University, Baltimore 21218, USA.

出版信息

Vis Neurosci. 1996 Mar-Apr;13(2):223-35. doi: 10.1017/s095252380000746x.

Abstract

Monocular deprivation in adult macaques produces a rapid down-regulation in GABA and GABAA receptor subunit immunoreactivity in deprived-eye columns of primary visual cortex (VI) but a significantly delayed GABA reduction in deprived layers of the dorsal lateral geniculate nucleus (LGN). These findings, suggesting that normal inhibitory neurotransmission persists in LGN at a time when VI inhibitory mechanisms are greatly altered, are consistent with physiological studies that have demonstrated a greater degree of functional plasticity in VI than in LGN. Nonetheless, functional adaptation to partial loss of visual input has been detected in the LGN, indicating that synaptic plasticity takes place in this nucleus. In the present study, evidence for early changes in inhibitory neurotransmission were examined with immunocytochemical methods to determine if, in the absence of early GABA regulation, GABAA receptor subunits in macaque LGN are affected by adult deprivation. Immunoreactivity for alpha 1 and beta 2/3 subunits of the GABAA receptor was intense within the magnocellular layers and more modest in the parvocellular layers and intercalated layers. In all layers, immunoreactivity was present in the cytoplasm and along the surfaces of relatively large somata and in dense tangles of processes in the neuropil. Double-labeling experiments demonstrated that somata and processes immunoreactive for alpha 1 and beta 2/3 were surrounded by GABA terminals but no cell intensely immunoreactive for either subunit expressed immunoreactivity for GABA, itself. Following periods of monocular deprivation by tetrodotoxin (TTX) injection for 4 days or longer, layers deprived of visual activity displayed levels of alpha 1 and beta 2/3 immunoreactivity markedly lower than those displayed by the adjacent, normally active layers. Such changes were greater as the period of deprivation increased. The changes included a loss of immunostaining in and around somata and in many neuropil elements of deprived layers. These data indicate that GABA and GABAA receptor subunits alpha 1 and beta 2/3 are expressed by separate populations of neurons in macaque LGN that are differentially regulated by visual activity. The findings suggest that rapid, activity-dependent regulation of postsynaptic receptors represents one mechanism for altering synaptic strength in the adult macaque visual system.

摘要

成年猕猴单眼剥夺会使初级视皮层(V1)被剥夺眼柱中的GABA和GABAA受体亚基免疫反应性迅速下调,但背外侧膝状核(LGN)被剥夺层中的GABA减少则明显延迟。这些发现表明,当V1抑制机制发生极大改变时,LGN中正常的抑制性神经传递仍持续存在,这与生理学研究结果一致,该研究表明V1的功能可塑性程度高于LGN。尽管如此,在LGN中已检测到对部分视觉输入丧失的功能适应性,表明该核中发生了突触可塑性。在本研究中,用免疫细胞化学方法检查了抑制性神经传递早期变化的证据,以确定在没有早期GABA调节的情况下,猕猴LGN中的GABAA受体亚基是否受成年期剥夺的影响。GABAA受体α1和β2/3亚基的免疫反应性在大细胞层中强烈,在小细胞层和插入层中较弱。在所有层中,免疫反应性存在于细胞质中、相对较大的胞体表面以及神经毡中密集的突起缠结处。双重标记实验表明,对α1和β2/3有免疫反应性的胞体和突起被GABA终末包围,但对任一亚基有强烈免疫反应性的细胞本身均不表达GABA免疫反应性。在通过注射河豚毒素(TTX)进行4天或更长时间的单眼剥夺后,失去视觉活动的层显示出的α1和β2/3免疫反应性水平明显低于相邻的正常活动层。随着剥夺时间的延长,这种变化更大。这些变化包括被剥夺层的胞体及其周围以及许多神经毡成分中的免疫染色丧失。这些数据表明,GABA以及GABAA受体亚基α1和β2/3由猕猴LGN中不同的神经元群体表达,且受视觉活动的差异调节。这些发现表明,突触后受体的快速、活动依赖性调节是成年猕猴视觉系统中改变突触强度的一种机制。

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