Distinct calcium sources support multiple modes of synaptic release from cranial sensory afferents

Jessica A. Fawley, Mackenzie E. Hofmann, Michael C. Andresen

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Most craniosensory afferents have unmyelinated axons expressing TRP Vanilloid 1 (TRPV1) receptors in synaptic terminals at the solitary tract nucleus (NTS). Neurotransmission from these synapses is characterized by substantial asynchronous EPSCs following action potential-synched EPSCs and high spontaneous rates that are thermally sensitive. The present studies blocked voltage-activated calciumchannels (CaV) usingthenonselectiveCaVblocker Cd2+ or thespecificN-typeblocker ω-conotoxinGVIAtoexaminethecalcium dependence of the synchronous, asynchronous, spontaneous, and thermally gated modes of release. In rat brainstem slices containing caudal NTS, shocks to the solitary tract (ST) triggered synchronous ST-EPSCs and trailing asynchronous EPSCs. Cd2+ or GVIA efficiently reduced both synchronous and asynchronous EPSCs without altering spontaneous or thermal-evoked transmission. Activation of TRPV1 with either the selective agonist resiniferatoxin (150 PM) or temperature augmented basal sEPSC rates but failed to alter the synchronous or asynchronous modes of release. These data indicate that calcium sourced through TRPV1 has no access to the synchronous or asynchronous release mechanism(s) and conversely that CaV-sourced calcium does not interact with the thermally evoked mode of release. Buffering intracellular calcium with EGTA-AM or BAPTA-AM reduced asynchronous EPSC rates earlier and to a greater extent than synchronous ST-EPSC amplitudes without altering sEPSCs or thermal sensitivity. Buffering therefore distinguishes asynchronous vesicles as possessing a highly sensitive calcium sensor located perhaps more distant from CaV than synchronous vesicles or thermally evoked vesicles from TRPV1. Together, our findings suggest separate mechanisms of release for spontaneous, asynchronous and synchronous vesicles that likely reside in unique, spatially separated vesicle domains.

Original languageEnglish (US)
Pages (from-to)8957-8966
Number of pages10
JournalJournal of Neuroscience
Issue number34
StatePublished - Aug 24 2016


  • Calcium
  • Nucleus of the solitary tract
  • Spontaneous release
  • Synaptic transmission
  • TRPV1
  • Unmyelinated

ASJC Scopus subject areas

  • General Neuroscience


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