Depolarization-induced suppression of inhibition  Depolarization-induced suppression of inhibition is the classical and original electrophysiological example of endocannabinoid function in the central nervous system. Prior to the demonstration that depolarization-induced suppression of inhibition was dependent on the cannabinoid CB1 receptor function, there was no way of producing an "in vitro" endocannabinoid mediated effect. Depolarization-induced suppression of inhibition is classically produced in a brain slice experiment (i.e. a 300-400 µm slice of brain, with intact axons and synapses) where a single neuron is "depolarized" (the normal −70 mV potential across the neuronal membrane is reduced, usually to −30 to 0 mV) for a period of 1 to 10 seconds. After the depolarization, inhibitory GABA mediated neurotransmission is reduced. This has been demonstrated to be caused by the release of endogenous cannabinoids from the depolarized neuron which diffuses to nearby neurons, and binds and activates CB1 receptors, which act presynaptically to reduce neurotransmitter release. Depolarization-induced suppression of inhibition was discovered in 1992 by Vincent et al., (1992) working in purkinje cells of the cerebellum then confirmed in the hippocampus by Pitler & Alger, 1992. These groups were studying the responses of large pyramidal projection neurons to GABA, the main inhibitory neurotransmitter in the central nervous system. GABA is typically released by small interneurons in many regions of the brain, where its job is to inhibit the activity of primary neurons, such as the CA1 pyramidal neurons of the hippocampus or the Purkinje cells of the cerebellum. Activation of GABA receptors on these cells, whether they are ionotropic or metabotropic, typically results in the influx of chloride ions into that target cell. This build-up of negative charge from the chloride ions results in the hyperpolarization of the target cell, making it less likely to fire an action potential. Accordingly, any ionic current that hyperpolarizes a cell is called an inhibitory current. In their experiments with projection neurons in the hippocampus and cerebellum, both groups noticed that a train of action potentials in these cells resulted in a temporary reduction in inhibitory currents caused by GABA-ergic interneurons. Since this reduction of inhibitory currents could be invoked simply by depolarization of the target cell, this phenomenon was termed depolarization-induced suppression of inhibition.