Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents

Mackenzie E. Hofmann, Michael Andresen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The recycling of vesicle membrane fused during exocytosis is essential to maintaining neurotransmission. The GTPase dynamin is involved in pinching off membrane to complete endocytosis and can be inhibited by dynasore resulting in activity-dependent depletion of release-competent synaptic vesicles. In rat brainstem slices, we examined the effects of dynasore on three different modes of glutamate release-spontaneous, evoked, and asynchronous release-at solitary tract (ST) inputs to neurons in the nucleus of the solitary tract (NTS). Intermittent bursts of stimuli to the ST interspersed with pauses in stimulation allowed examination of these three modes in each neuron continuously. Application of 100 μM dynasore rapidly increased the spontaneous EPSC (sEPSC) frequency which was followed by inhibition of both ST-evoked EPSCs (ST-EPSC) as well as asynchronous EPSCs. The onset of ST-EPSC failures was not accompanied by amplitude reduction-a pattern more consistent with conduction block than reduced probability of vesicle release. Neither result suggested that dynasore interrupted endocytosis. The dynasore response profile resembled intense presynaptic TRPV1 activation. The TRPV1 antagonist capsazepine failed to prevent dynasore increases in sEPSC frequency but did prevent the block of the ST-EPSC. In contrast, the TRPV1 antagonist JNJ 17203212 prevented both actions of dynasore in neurons with TRPV1-expressing ST inputs. In a neuron lacking TRPV1- expressing ST inputs, however, dynasore promptly increased sEPSC rate followed by block of ST-evoked EPSCs. Together our results suggest that dynasore actions on ST-NTS transmission are TRPV1-independent and changes in glutamatergic transmission are not consistent with changes in vesicle recycling and endocytosis.

Original languageEnglish (US)
Article numbere0174915
JournalPLoS One
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Visceral Afferents
synaptic transmission
Synaptic Transmission
endocytosis
neurons
recycling
antagonists
Neurons
Endocytosis
exocytosis
guanosinetriphosphatase
brain stem
Recycling
glutamates
Dynamins
Membranes
N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
rats
Solitary Nucleus
Synaptic Vesicles

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents. / Hofmann, Mackenzie E.; Andresen, Michael.

In: PLoS One, Vol. 12, No. 3, e0174915, 01.03.2017.

Research output: Contribution to journalArticle

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