title: TRPV1 marks synaptic segregation of multiple convergent afferents at the rat medial solitary tract nucleus.
abstract: TRPV1 receptors are expressed on most but not all central terminals of cranial visceral afferents in the caudal solitary tract nucleus (NTS). TRPV1 is associated with unmyelinated C-fiber afferents. Both TRPV1+ and TRPV1- afferents enter NTS but their precise organization remains poorly understood. In horizontal brainstem slices, we activated solitary tract (ST) afferents and recorded ST-evoked glutamatergic excitatory synaptic currents (ST-EPSCs) under whole cell voltage clamp conditions from neurons of the medial subnucleus. Electrical shocks to the ST produced fixed latency EPSCs (jitter<200 µs) that identified direct ST afferent innervation. Graded increases in shock intensity often recruited more than one ST afferent and ST-EPSCs had consistent threshold intensity, latency to onset, and unique EPSC waveforms that characterized each unitary ST afferent contact. The TRPV1 agonist capsaicin (100 nM) blocked the evoked TRPV1+ ST-EPSCs and defined them as either TRPV1+ or TRPV1- inputs. No partial responses to capsaicin were observed so that in NTS neurons that received one or multiple (2-5) direct ST afferent inputs--all were either blocked by capsaicin or were unaltered. Since TRPV1 mediates asynchronous release following TRPV1+ ST-evoked EPSCs, we likewise found that recruiting more than one ST afferent further augmented the asynchronous response and was eliminated by capsaicin. Thus, TRPV1+ and TRPV1- afferents are completely segregated to separate NTS neurons. As a result, the TRPV1 receptor augments glutamate release only within unmyelinated afferent pathways in caudal medial NTS and our work indicates a complete separation of C-type from A-type afferent information at these first central neurons.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon, United States of America.
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: Michael C
authors.initials: MC
authors.lastname: Andresen
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism*; D017833:Visceral Afferents / Q000187:drug effects
chemical_list: D017470:Receptors, Glutamate; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D018698:Glutamic Acid; D002211:Capsaicin