Effects of TRPV1 activation on synaptic excitation in the dentate gyrus of a mouse model of temporal lobe epilepsy

Muthu D. Bhaskaran, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Temporal lobe epilepsy (TLE) is a condition characterized by an imbalance between excitation and inhibition in the temporal lobe. Hallmarks of this change are axon sprouting and accompanying synaptic reorganization in the temporal lobe. Synthetic and endogenous cannabinoids have variable therapeutic potential in treating intractable temporal lobe epilepsy, in part because cannabinoid ligands can bind multiple receptor types. This study utilized in vitro electrophysiological methods to examine the effect of transient receptor potential vanilloid type 1 (TRPV1) activation in dentate gyrus granule cells in a murine model of TLE. Capsaicin, a selective TRPV1 agonist had no measurable effect on overall synaptic input to granule cells in control animals, but significantly enhanced spontaneous and miniature EPSC frequency in mice with TLE. Exogenous application of anandamide, an endogenous cannabinoid that acts at both TRPV1 and cannabinoid type 1 receptors (CB1R), also enhanced glutamate release in the presence of a CB1R antagonist. Anandamide reduced the EPSC frequency when TRPV1 were blocked with capsazepine. Western blot analysis of TRPV1 receptor indicated protein expression was significantly greater in the dentate gyrus of mice with TLE compared with control mice. This study indicates that a prominent cannabinoid agonist can increase excitatory circuit activity in the synaptically reorganized dentate gyrus of mice with TLE by activating TRPV1 receptors, and suggests caution in designing anticonvulsant therapy based on modulating the endocannabinoid system.

Original languageEnglish
Pages (from-to)529-536
Number of pages8
JournalExperimental Neurology
Volume223
Issue number2
DOIs
StatePublished - Jun 2010

Bibliographical note

Funding Information:
Funded by grants from the NIH ( R21 NS052302 ) and the Epilepsy Foundation .

Keywords

  • Anandamide
  • Endocannabinoid
  • Mossy fiber sprouting
  • Seizure
  • VR1
  • Vanilloid

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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