Puente Nagore, Reguero Leire, Elezgarai Izaskun, Canduela Miren-Josune, Mendizabal-Zubiaga Juan, Ramos-Uriarte Almudena, Fernández-Espejo Emilio, Grandes Pedro
Department of Neurosciences, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, 48940, Leioa, Spain.
Brain Struct Funct. 2015 Mar;220(2):1187-94. doi: 10.1007/s00429-014-0711-2. Epub 2014 Feb 1.
The transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel that plays an important role in pain perception and modulates neurotransmitter release and synaptic plasticity in the brain. TRPV1 function must lay on its anatomical distribution in the peripheral and central nervous system regions involved in the physiological roles of the channel. However, the anatomical localization of TRPV1 is well established in the periphery, but in the brain it is a matter of debate. While some studies support the presence of TRPV1 in several brain regions, recent evidences suggest a restricted distribution of the channel in the central nervous system. To investigate to what extent central TRPV1 function stands on a precise brain distribution of the channel, we examined the mouse hippocampal dentate molecular layer (ML) where TRPV1 mediates long-term synaptic plasticity. Using pre-embedding immunocytochemistry for high resolution electron microscopy, we show that TRPV1 immunoparticles are highly concentrated in postsynaptic dendritic spines to asymmetric perforant path synapses in the outer 2/3 of the ML. However, TRPV1 is poorly expressed at the excitatory hilar mossy cell synapses in the inner 1/3 of this layer. Importantly, the TRPV1 pattern distribution disappeared in the ML of TRPV1-knockout mice. Taken together, these findings support the notion of the presence of TRPV1 in a brain region where the channel has been shown to have a functional role, such as the perforant path synapses in the hippocampal dentate ML.
瞬时受体电位香草酸亚型1(TRPV1)是一种非选择性阳离子通道,在疼痛感知中起重要作用,并调节大脑中的神经递质释放和突触可塑性。TRPV1的功能必须依赖于其在参与该通道生理作用的外周和中枢神经系统区域的解剖分布。然而,TRPV1在外周的解剖定位已明确,但在大脑中的定位仍存在争议。虽然一些研究支持TRPV1在几个脑区存在,但最近的证据表明该通道在中枢神经系统中的分布有限。为了研究中枢TRPV1功能在多大程度上依赖于该通道在大脑中的精确分布,我们检查了小鼠海马齿状分子层(ML),其中TRPV1介导长期突触可塑性。使用预包埋免疫细胞化学进行高分辨率电子显微镜检查,我们发现TRPV1免疫颗粒高度集中在ML外2/3的突触后树突棘至不对称穿通路径突触处。然而,在该层内1/3的兴奋性门区苔藓细胞突触处,TRPV1表达较弱。重要的是,TRPV1基因敲除小鼠的ML中TRPV1的模式分布消失。综上所述,这些发现支持了TRPV1存在于已证明该通道具有功能作用的脑区的观点,例如海马齿状ML中的穿通路径突触。