Resumen
[EN] The transient receptor potential vanilloid 1 (TRPV1) participates in synaptic functions
in the brain. In the dentate gyrus, post-synaptic TRPV1 in the granule cell (GC)
dendritic spines mediates a type of long-term depression (LTD) of the excitatory
medial perforant path (MPP) synapses independent of pre-synaptic cannabinoid CB1
receptors. As CB1 receptors also mediate LTD at these synapses, both CB1 and
TRPV1 might be influencing the activity of each other acting from opposite synaptic
sites. We tested this hypothesis in the MPP–GC synapses of mice lacking TRPV1
(TRPV1-/-). Unlike wild-type (WT) mice, low-frequency stimulation (10min at 10Hz)
of TRPV1-/- MPP fibers elicited a form of long-term potentiation (LTP) that was
dependent on (1) CB1 receptors, (2) the endocannabinoid 2-arachidonoylglycerol
(2-AG), (3) rearrangement of actin filaments, and (4) nitric oxide signaling. These
functional changes were associated with an increase in the maximum binding
efficacy of guanosine-5′-O-(3-[35S]thiotriphosphate) ([35S]GTPgS) stimulated by the CB1
receptor agonist CP 55,940, and a significant decrease in receptor basal activation
in the TRPV1-/- hippocampus. Finally, TRPV1-/- hippocampal synaptosomes showed
an augmented level of the guanine nucleotide-binding (G) Gai1, Gai2, and Gai3 protein
alpha subunits. Altogether, the lack of TRPV1 modifies CB1 receptor signaling in the
dentate gyrus and causes the shift from CB1 receptor-mediated LTD to LTP at the
MPP–GC synapses.