Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning
Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning
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DOI：
10.1073/pnas.1525586113
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发表时间：
2016-03-08
影响因子：
11.1
通讯作者：
Becamel, Carine
中科院分区：
文献类型：
--
作者：
Barre, Alexander;Berthoux, Coralie;Becamel, Carine
更高层次的认知过程强烈依赖于丘脑背内侧核和前额叶皮质（PFC）之间复杂的相互作用。丘脑额叶连接性改变与精神分裂症认知功能障碍有关。前额叶5-羟色胺（5-HT）（2A）受体在皮层网络活动中起着重要作用，但其调节丘脑-皮层突触的神经递质传递和可塑性的机制仍在很大程度上尚未探索。在这里，我们发现，5-HT 2A受体激活增强NMDA的传输和门的诱导的时间依赖性可塑性的NMDA受体介导的丘脑皮质突触在急性PFC切片。表达5-HT 2A受体在内侧背丘脑（突触前网站）的5-HT 2A受体缺陷小鼠，但不是在PFC（突触后网站），使用病毒基因传递方法，挽救了否则缺乏增强NMDA传输，诱导时间可塑性，并在联想记忆的赤字。据我们所知，这些结果提供了第一个生理证据的作用，突触前5-HT 2A受体位于丘脑皮质突触的控制丘脑额叶连接和相关的认知功能。
Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)(2A) receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. Here, we show that 5-HT2A receptor activation enhances NMDA transmission and gates the induction of temporal-dependent plasticity mediated by NMDA receptors at thalamocortical synapses in acute PFC slices. Expressing 5-HT2A receptors in the mediodorsal thalamus (presynaptic site) of 5-HT2A receptor-deficient mice, but not in the PFC (postsynaptic site), using a viral gene-delivery approach, rescued the otherwise absent potentiation of NMDA transmission, induction of temporal plasticity, and deficit in associative memory. These results provide, to our knowledge, the first physiological evidence of a role of presynaptic 5-HT2A receptors located at thalamocortical synapses in the control of thalamofrontal connectivity and the associated cognitive functions.