TRPV1 Modulation of Plasticity in the Hippocampus
Walther, Curtis; Mors, M.; Blickenstaff, J.; Nelson, B.; Daniel, S.; Castle, M.; Crouch, J.; Jensen, T.; Bennion, D.; Edwards, J. G.
Learning and memory are phenomena made possible via physical changes at neuronal synapses in the brain, a process known as synaptic plasticity. Dysfunctions in synaptic plasticity contribute to such diseases and disorders as Alzheimer's Disease, Parkinson's Disease, and retrograde amnesia (Brunetal., 2001). Recently, TRPV1 activation was shown to mediate synaptic plasticity in the hippocampus (Gibsonetal., 2008). TRPV1 is a presynaptic ligand-gated calcium (Ca2+) channel located throughout the CNS, including in the hippocampus. TRPV1 channels are activated by the binding of capsaicin, which is responsible for producing the “heat” of red peppers. Several studies implicate a role for TRPV1 in contextual fear learning (Marschetal., 2007), recall of spatial memory (Lietal., 2008), and anxiety-related disorders (Santosetal., 2007), including depression (Kasckowetal. 2004). Using field electrophysiolgical recordings in CA1 stratum radiatum we measured high frequency stimulation or the taburst-induced LTP in the presence and absence of TRPV1 agonists, TRPV1 antagonist and picrotoxin. Our data suggest that TRPV1 receptors mediating increased LTP are not expressed at theCA3-A1synapse, but possibly at the CA3 interneuron synapse. Further, we propose a novel mechanism by which TRPV1 activation enhances hippocampal CA1 pyramidal cell LTP via modulation of an inhibitory interneuron circut.