• asynchronous;
  • cannabinoid receptors;
  • cholecystokinin;
  • interneurons;
  • tonic inhibition


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 μm), 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 μm) 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.