The transient receptor potential vanilloid-1 is localized at excitatory synapses in the mouse dentate gyrus

Abstract

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.

Compartment-Specific Modulation of GABAergic Synaptic Transmission by TRPV1 Channels in the Dentate Gyrus

“…The results presented in this study demonstrate that TRPV1 channels, in addition to modulating excitatory synaptic inputs (Chávez et al, 2010;Grueter et al, 2010;Puente et al, 2011), can also target inhibitory synapses in rat and mouse DG. We report that activation of TRPV1 channels, presumably by promoting internalization of GABA A Rs, selectively depresses somatic but not dendritic GABAergic synaptic inputs onto DGCs.…”

“…Our finding that TRPV1 channels suppress somatic but not dendritic inhibitory inputs (Figs. 1, 2) is reminiscent of previous observations showing that the TRPV1-mediated depression of excitatory transmission occurs at some synaptic inputs but not others (Chávez et al, 2010;Grueter et al, 2010;Puente et al, 2011). Thus, input specificity could be a general property of TRPV1-mediated effects throughout the brain.…”

“…For example, it could reflect the selective expression of TRPV1 channels at some synapses, although spatially constrained signaling downstream of TRPV1 channels may also contribute. In support of TRPV1 synaptic segregation, a recent anatomical immunoelectron microscopy study in DG showed that TRPV1 is highly concentrated in postsynaptic dendritic spines receiving perforant path inputs, whereas expression is weak at more proximal excitatory hilar mossy cell synapses (Puente et al, 2014). This subcellular anatomical distribution is consistent with the selective TRPV1-mediated suppression of excitatory transmission at medial perforant path but not hilar mossy cell synapses (Chávez et al, 2010).…”

“…Li et al, 2004;Roberts et al, 2004;Tó th et al, 2005;Cristino et al, 2006;Marsch et al, 2007;Gibson et al, 2008;H.B. Li et al, 2008;Maccarrone et al, 2008;Aguiar et al, 2009;Maione et al, 2009;Musella et al, 2009Musella et al, , 2010Chávez et al, 2010;Grueter et al, 2010;Bennion et al, 2011;Puente et al, 2011Puente et al, , 2014P. Han et al, 2013;Terzian et al, 2014).…”

“…Of note, a recent report suggests that TRPV1 channels are restricted to a few brain areas (Cavanaugh et al, 2011). Thus far, most work in the brain has focused on the role of TRPV1 channels at excitatory synapses where their activation can modify synaptic transmission via both presynaptic (Marinelli et al, 2002(Marinelli et al, , 2003Gibson et al, 2008;Musella et al, 2009;Köles et al, 2013) and postsynaptic mechanisms (Chávez et al, 2010;Grueter et al, 2010;Puente et al, 2011;Kim et al, 2012). However, the role of TRPV1 channels at inhibitory synapses remains poorly understood.…”