Depolarization-induced suppression of inhibition was thought to be due to a reduction in pre-synaptic neurotransmitter release for 2 reasons. 1) The magnitudes of spontaneously evoked inhibitory post-synaptic currents (IPSCs), caused by the release of a single pre-synaptic vesicle filled with GABA, remained unchanged and 2) The cellular responses to exogenously applied GABA remained the same. These observations suggested that no changes occurred in the post-synaptic cell to change its responsiveness to GABA during depolarization-induced suppression of inhibition. Somehow, depolarization-induced suppression of inhibition appeared to be mediated by a retrograde synaptic messenger whose synthesis or release was stimulated by the depolarization of the target cell. This messenger then diffused "backwards" to the pre-synaptic cell, where it caused a reduction in neurotransmitter release.