Asynchronous release of GABA via tonic cannabinoid receptor activation at identified interneuron synapses in rat CA1

Eur J Neurosci. 2010 Apr;31(7):1196-207. doi: 10.1111/j.1460-9568.2010.07165.x. Epub 2010 Mar 19.

Abstract

The influence of local circuit interneurons is thought to play an important role in adjusting synaptic strength via endogenous cannabinoid type 1 (CB1) receptors. Using paired whole-cell recordings, combined with double immunofluorescence and biocytin labelling in acute slices of rat CA1 at postnatal day 18-23, we investigated the properties of Cholecystokinin (CCK)-positive stratum radiatum local circuit interneuron connections that utilised CB1 receptors. Three types of synaptic connections were studied, lacunosum-moleculare-radiatum perforant path-associated (LM-R PPA) to Shaffer collateral-associated (SCA) interneurons, SCA-SCA interneurons and SCA-pyramidal cells. These three synapses were differentially under tonic reduction of inhibition that was blocked by the CB1 receptor inverse agonist AM-251 (10 microM), which enhanced IPSPs. The strength of tonic reduction of inhibition was correlated with asynchronous release which was apparent at connections among interneurons. AM-251 increased the ratio of synchronous to asynchronous release (synchronicity ratio), while the CB receptor agonist anandamide (14 microM) decreased the synchronicity ratio. Fast and slow calcium chelators (BAPTA-AM and EGTA-AM) also increased the synchronicity ratio, accelerated inhibitory time courses and reduced IPSP amplitudes. These data suggest that CB1 receptors at connections among interneuron synapses play a role in tonic suppression of inhibition and govern the asynchronous release of GABA, modulating the time windows of inhibition. Effects of calcium chelators suggest that asynchronous release is a result of a long-lasting presynaptic calcium transients and/or a large distance between calcium source and sensor of exocytosis. These properties of specialised inhibitory neurons may have important modulatory roles in controlling spike timing among local circuit interneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Arachidonic Acids / pharmacology
  • CA1 Region, Hippocampal / cytology*
  • Cannabinoid Receptor Modulators / pharmacology
  • Chelating Agents / pharmacology
  • Cholecystokinin / metabolism
  • Dendrites / drug effects
  • Dendrites / physiology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Endocannabinoids
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Interneurons / cytology*
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Male
  • Neural Inhibition / physiology
  • Neural Pathways / physiology
  • Patch-Clamp Techniques / methods
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Synapses / metabolism*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Chelating Agents
  • Endocannabinoids
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • AM 251
  • Egtazic Acid
  • gamma-Aminobutyric Acid
  • Cholecystokinin
  • EGTA acetoxymethyl ester
  • biocytin
  • Lysine
  • anandamide