At many synapses, and at physiological temperature, the entire sequence of events takes place in < 1 ms. In particular, one subtype of GABAergic cells, the fast-spiking, parvalbumin (PV)-expressing interneuron, releases the neurotransmitter very rapidly and with high temporal precision (Kraushaar & Jonas, 2000). Other types of synapses release neurotransmitters more asynchronously, FG-4592 purchase especially during and after trains of

stimuli (Barrett & Stevens, 1972; Goda & Stevens, 1994; Atluri & Regehr, 1998). In particular, asynchronous release is very prominent at the output synapses of hippocampal interneurons containing the neuropeptide cholecystokinin (CCK) (Hefft & Jonas, 2005; Daw et al., 2009; Karson et al., 2009). Thus, whereas synchrony of transmitter

release is a hallmark property of transmission at PV-interneurons, asynchrony of release characterizes CCK-interneurons. In addition to these differences in the time course of neurotransmitter release, CCK-interneurons differ from PV-interneurons in several ways. Whereas PV-interneurons exclusively use P/Q-type Ca2+ channels for transmitter release, CCK-interneurons rely on N-type Ca2+ channels (Hefft & Jonas, 2005). Furthermore, whereas PV-interneurons have presynaptic terminals endowed with M2 muscarinic acetylcholine and μ opioid receptors, the terminals of CCK-interneurons express cannabinoid (CB1) receptors (Freund

& Katona, 2007). Importantly, CB1 receptors situated on the presynaptic terminals find more of CCK-interneurons mediate depolarization-induced suppression of inhibition (DSI), a form of short-term synaptic plasticity induced by depolarization of postsynaptic cells (Pitler & Alger, 1994; Wilson et al., 2001). This depolarization induces endocannabinoid synthesis and release from the postsynaptic cell, leading to activation of CB1 receptors, which transiently blocks transmitter release from the presynaptic terminals. Asynchronous GABA release was originally reported at output synapses of CCK-interneurons on principal cells (Hefft & Jonas, 2005). Whether asynchronous release also G protein-coupled receptor kinase occurs at connections between CCK-interneurons and other interneurons has remained unclear. Three recent publications shed light on this question, using paired recordings between synaptically connected neurons. Daw et al. (2009) examined synapses between CCK-interneurons in the hippocampal CA3 and CA1 region. Karson et al. (2009) demonstrated asynchronous release at synapses between CCK-interneurons and PV-interneurons in CA1. Finally, in this issue of EJN, Ali & Todorova (2010) studied synapses between CCK-interneurons in the stratum lacunosum moleculare-radiatum (LM-R) of the CA1 subfield, a region highly enriched in CCK-immunoreactive cells.