Axonal conduction block as a novel mechanism of prepulse inhibition

In prepulse inhibition (PPI), the startle response to a strong, unexpected stimulus is diminished if shortly preceded by the onset of a different stimulus. Because deficits in this inhibitory gating process are a hallmark feature of schizophrenia and certain other psychiatric disorders, the mechanisms underlying PPI are of significant interest. We previously used the invertebrate model system Tritonia diomedea to identify the first cellular mechanism for PPI--presynaptic inhibition of transmitter release from the afferent neurons (S-cells) mediating the startle response. Here, we report the involvement of a second, more powerful PPI mechanism in Tritonia: prepulse-elicited conduction block of action potentials traveling in the startle pathway caused by identified inhibitory interneurons activated by the prepulse. This example of axo-axonic conduction block--neurons in one pathway inhibiting the propagation of action potentials in another--represents a novel and potent mechanism of sensory gating in prepulse inhibition.