Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses

Elife. 2020 May 13:9:e52852. doi: 10.7554/eLife.52852.

Abstract

Synaptic transmission is initiated via spontaneous or action-potential evoked fusion of synaptic vesicles. At excitatory synapses, glutamatergic receptors activated by spontaneous and evoked neurotransmission are segregated. Although inhibitory synapses also transmit signals spontaneously or in response to action potentials, they differ from excitatory synapses in both structure and function. Therefore, we hypothesized that inhibitory synapses may have different organizing principles. We report picrotoxin, a GABAAR antagonist, blocks neurotransmission in a use-dependent manner at rat hippocampal synapses and therefore can be used to interrogate synaptic properties. Using this tool, we uncovered partial segregation of inhibitory spontaneous and evoked neurotransmission. We found up to 40% of the evoked response is mediated through GABAARs which are only activated by evoked neurotransmission. These data indicate GABAergic spontaneous and evoked neurotransmission processes are partially non-overlapping, suggesting they may serve divergent roles in neuronal signaling.

Keywords: GABAergic neurotransmission; neuroscience; picrotoxin; rat; spontaneous release.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Electric Stimulation
  • Female
  • GABA Antagonists / pharmacology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials* / drug effects
  • Neural Inhibition* / drug effects
  • Picrotoxin / pharmacology
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism
  • Synaptic Transmission* / drug effects

Substances

  • GABA Antagonists
  • Receptors, GABA-A
  • Picrotoxin