TY - JOUR
T1 - TRPV1 Channels Mediate Long-Term Depression at Synapses on Hippocampal Interneurons
AU - Gibson, Helen E.
AU - Edwards, Jeffrey G.
AU - Page, Rachel S.
AU - Van Hook, Matthew J.
AU - Kauer, Julie A.
N1 - Funding Information:
The authors thank Barry Connors and Robert Malenka as well as members of our lab for helpful discussions and reading of the manuscript, Kevin Gormley at NIDA for providing SR141716A, and Jeannette Downing-Park for technical assistance. This work was supported by National Institutes of Health grants DA11289, NS050570 (J.A.K.), and NS049779 (J.G.E.).
PY - 2008/3/13
Y1 - 2008/3/13
N2 - TRPV1 receptors have classically been defined as heat-sensitive, ligand-gated, nonselective cation channels that integrate nociceptive stimuli in sensory neurons. TRPV1 receptors have also been identified in the brain, but their physiological role is poorly understood. Here we report that TRPV1 channel activation is necessary and sufficient to trigger long-term synaptic depression (LTD). Excitatory synapses onto hippocampal interneurons were depressed by either capsaicin, a potent TRPV1 channel activator, or the endogenously released eicosanoid, 12-(S)-HPETE, whereas neighboring excitatory synapses onto CA1 pyramidal cells were unaffected. TRPV1 receptor antagonists also prevented interneuron LTD. In brain slices from TRPV1-/- mice, LTD was absent, and neither capsaicin nor 12-(S)-HPETE elicited synaptic depression. Our results suggest that, in the hippocampus, TRPV1 receptor activation selectively modifies synapses onto interneurons. Like other forms of hippocampal synaptic plasticity, TRPV1-mediated LTD may have a role in long-term changes in physiological and pathological circuit behavior during learning and epileptic activity.
AB - TRPV1 receptors have classically been defined as heat-sensitive, ligand-gated, nonselective cation channels that integrate nociceptive stimuli in sensory neurons. TRPV1 receptors have also been identified in the brain, but their physiological role is poorly understood. Here we report that TRPV1 channel activation is necessary and sufficient to trigger long-term synaptic depression (LTD). Excitatory synapses onto hippocampal interneurons were depressed by either capsaicin, a potent TRPV1 channel activator, or the endogenously released eicosanoid, 12-(S)-HPETE, whereas neighboring excitatory synapses onto CA1 pyramidal cells were unaffected. TRPV1 receptor antagonists also prevented interneuron LTD. In brain slices from TRPV1-/- mice, LTD was absent, and neither capsaicin nor 12-(S)-HPETE elicited synaptic depression. Our results suggest that, in the hippocampus, TRPV1 receptor activation selectively modifies synapses onto interneurons. Like other forms of hippocampal synaptic plasticity, TRPV1-mediated LTD may have a role in long-term changes in physiological and pathological circuit behavior during learning and epileptic activity.
KW - MOLNEURO
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U2 - 10.1016/j.neuron.2007.12.027
DO - 10.1016/j.neuron.2007.12.027
M3 - Article
C2 - 18341994
AN - SCOPUS:40249111593
VL - 57
SP - 746
EP - 759
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 5
ER -