Visualization by high resolution immunoelectron microscopy of the transient receptor potential vanilloid-1 at inhibitory synapses of the mouse dentate gyrus.

Miren-Josune Canduela,Leire Reguero,Almudena Ramos-Uriarte,Juan Mendizabal-Zubiaga,Izaskun Elezgarai,Pedro Grandes,Inmaculada Gerrikagoitia,Nagore Puente,Andrej A Romanovsky

doi:10.1371/journal.pone.0119401

Abstract

We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1), a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the hippocampal dentate molecular layer (ML). In the present work, we have studied the distribution of TRPV1 at inhibitory synapses in the ML. With this aim, a preembedding immunogold method for high resolution electron microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically (∼60% of total immunoparticles) at postsynaptic dendritic membranes receiving symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution is not observed in the ML of TRPV1 knock-out mice. These findings extend the knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the dentate molecular layer where the channel, in addition to excitatory synapses, is present.

Highlights

TRPV1 plays an important role in peripheral pain perception and modulates neurotransmitter release and synaptic plasticity in the brain
Silver-intensified TRPV1 immunoparticles were revealed in thick postsynaptic dendrites receiving symmetric synapses in the dentate molecular layer (ML) (Figs. 1A, B; 2A-C; 3A-D)
We used a highly sensitive preembedding immunogold method for electron microscopy to elucidate whether TRPV1 is present at inhibitory synapses, in particular, in the dentate gyrus

Summary

Introduction

TRPV1 plays an important role in peripheral pain perception and modulates neurotransmitter release and synaptic plasticity in the brain. It is a ligand-gated nonselective cationic channel activated by high temperature, low pH, some natural products (resiniferatoxin, capsaicin) and endogenous lipids or endovanilloids [1,2,3,4,5]. A wide central distribution of TRPV1 has been questioned because TRPV1 reporter mice showed a restricted TRPV1 brain expression that it is conserved from

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