Self-tuning of inhibition by endocannabinoids shapes spike-time precision in CA1 pyramidal neurons.
Dubruc F., Dupret D., Caillard O.
In the hippocampus, activity-dependent changes of synaptic transmission and spike-timing coordination are thought to mediate information processing for the purpose of memory formation. Here, we investigated the self-tuning of intrinsic excitability and spiking reliability by CA1 hippocampal pyramidal cells via changes of their GABAergic inhibitory inputs and endocannabinoid (eCB) signaling. Firing patterns of CA1 place cells, when replayed in vitro, induced an eCB-dependent transient reduction of spontaneous GABAergic activity, sharing the main features of depolarization-induced suppression of inhibition (DSI), and conditioned a transient improvement of spike-time precision during consecutive burst discharges. When evaluating the consequences of DSI on excitatory postsynaptic potential (EPSP)-spike coupling, we found that transient reductions of uncorrelated (spontaneous) or correlated (feedforward) inhibition improved EPSP-spike coupling probability. The relationship between EPSP-spike-timing reliability and inhibition was, however, more complex: transient reduction of correlated (feedforward) inhibition disrupted or improved spike-timing reliability according to the initial spike-coupling probability. Thus eCB-mediated tuning of pyramidal cell spike-time precision is governed not only by the initial level of global inhibition, but also by the ratio between spontaneous and feedforward GABAergic activities. These results reveal that eCB-mediated self-tuning of spike timing by the discharge of pyramidal cells can constitute an important contribution to place-cell assemblies and memory formation in the hippocampus.