title: Transient receptor potential vanilloid 1 agonists modulate hippocampal CA1 LTP via the GABAergic system.
abstract: Transient receptor potential vanilloid 1 (TRPV1) was shown to modulate hippocampal CA1 pyramidal cell synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Synaptic plasticity is the cellular mechanism thought to mediate declarative learning and memory in the hippocampus. Although TRPV1 is involved in modulating hippocampal plasticity, it has yet to be determined how TRPV1 mediates its effects. Using field electrophysiology in hippocampal CA1 stratum radiatum we investigated how TRPV1 agonists modulate LTP, low frequency stimulation-induced LTD, and (RS)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD. First we confirmed that TRPV1 agonists induce enhancement of CA1 pyramidal cell LTP in the absence the GABA(A) receptor antagonist picrotoxin. Because it was recently determined that TRPV1 mediates a novel form of LTD in CA1 inhibitory GABAergic interneurons, which can disinhibit CA1 pyramidal cells, we used picrotoxin to block the effect of the GABAergic circuitry on CA1 LTP. When using picrotoxin, the TRPV1 agonist-induced enhancement of CA1 LTP was eliminated suggesting that the GABAergic circuitry is required for TRPV1 agonist mediated increases. Regarding LTD, in contrast to previously reported data, we did not see TRPV1 agonist-mediated effect on low frequency-induced stimulus LTD. However, during DHPG-induced LTD, TRPV1 was involved in the acute, but not the long-term depression phase of this plasticity. In summary, our findings support TRPV1 agonist involvement in hippocampal synaptic plasticity, including its enhancement of CA1 LTP. We demonstrate that the enhancement mediated by TRPV1 agonists requires GABA input to pyramidal cells thus providing a mechanism for how TRPV1 agonists modulate hippocampal synaptic plasticity.
authors.affiliation: Brigham Young University, Department of Physiology and Developmental Biology, Provo, UT 84602, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Bennion
authors.forename: Tyron
authors.initials: T
authors.lastname: Jensen
authors.forename: Curtis
authors.initials: C
authors.lastname: Walther
authors.forename: John
authors.initials: J
authors.lastname: Hamblin
authors.forename: Andrew
authors.initials: A
authors.lastname: Wallmann
authors.forename: Jason
authors.initials: J
authors.lastname: Couch
authors.forename: Jacob
authors.initials: J
authors.lastname: Blickenstaff
authors.forename: Michael
authors.initials: M
authors.lastname: Castle
authors.forename: Lauren
authors.initials: L
authors.lastname: Dean
authors.forename: Sam
authors.initials: S
authors.lastname: Beckstead
authors.forename: Collin
authors.initials: C
authors.lastname: Merrill
authors.forename: Casey
authors.initials: C
authors.lastname: Muir
authors.forename: Teresa
authors.initials: T
authors.lastname: St Pierre
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.forename: Stephen
authors.initials: S
authors.lastname: Daniel
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Edwards
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000819:agonists* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; C010117:3,4-dihydroxyphenylglycol