Precise Synchrony by Mutual Inhibition: Experiments Vindicate Theory

Whether the timing of action potentials in the brain is semi-random, or is a “temporal code” that carries information, is a long-standing debate in neuroscience. One potential form of temporal coding is sharp synchrony between action potentials in different neurons, at the near-millisecond or sub-millisecond scale. Such synchrony has been observed in a few brain areas (retina, thalamus, cortex), and has been attributed either to electrical coupling by gap junctions or to shared excitatory inputs. Theoretical studies and computer models suggest that precise synchrony can also arise from reciprocal inhibitory synapses; however, this has not been confirmed experimentally. We recorded simultaneous spike trains from pairs of mouse cortical inhibitory interneurons connected by inhibitory synapses, either during epochs of network activity, or when the two interneurons were depolarized in isolation, and observed precise, sub-millisecond firing synchrony, even when the neurons were not coupled electrically. The degree of synchrony correlated with the strength of the inhibitory connection, and synchrony persisted when ionotropic glutamate receptors were blocked but was strongly reduced by blocking GABAA receptors. We conclude that mutual inhibition can drive precise firing synchrony in the absence of electrical coupling and shared excitatory inputs, as predicted theoretically.