title: Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons.
abstract: TRPV1 receptors feature prominently in nociception of spinal primary afferents but are also expressed in unmyelinated cranial visceral primary afferents linked to homeostatic regulation. Cranial visceral afferents enter the brain at the solitary tract nucleus (NTS) to control the heart, lungs, and other vital organs. Here we identify a role for central TRPV1 in the activity-dependent facilitation of glutamatergic transmission from solitary tract (ST) afferents. Fast, synchronous ST-NTS transmission from capsaicin-sensitive (TRPV1+) and -insensitive (TRPV1-) afferents was similar. However, afferent activation triggered long-lasting asynchronous glutamate release only from TRPV1+ synapses. Asynchronous release was proportional to synchronous EPSC amplitude, activity, and calcium entry. TRPV1 antagonists and low temperature blocked asynchronous release, but not evoked EPSCs. At physiological afferent frequencies, asynchronous release strongly potentiated the duration of postsynaptic spiking. This activity-dependent TPRV1-mediated facilitation is a form of synaptic plasticity that brings a unique central integrative feature to the CNS and autonomic regulation.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Peters
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: McDougall
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Fawley
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
authors.forename: Michael C
authors.initials: MC
authors.lastname: Andresen
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology
chemical_list: D000813:Anilides; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; D002211:Capsaicin