Axonal and somatic filtering of antidromically evoked cortical excitation by simulated deep brain stimulation in rat brain

Antidromic cortical excitation has been implicated as a contributing mechanism for high-frequency deep brain stimulation (DBS). Here, we examined the reliability of antidromic responses of type 2 corticofugal fibres in rat over a stimulation frequency range compatible to the DBS used in humans. We activated antidromically individual layer V neurones by stimulating their two subcortical axonal branches. We found that antidromic cortical excitation is not as reliable as generally assumed. Whereas the fast conducting branches of a type 2 axon in the highly myelinated brainstem region follow high-frequency stimulation, the slower conducting fibres in the poorly myelinated thalamic region function as low-pass filters. These fibres fail to transmit consecutive antidromic spikes at the beginning of high-frequency stimulation, but are able to maintain a steady low-frequency (6-12 Hz) spike output during the stimulation. In addition, antidromic responses evoked from both branches are rarely present in cortical neurones with a more hyperpolarized membrane potential. Our data indicate that axon-mediated antidromic excitation in the cortex is strongly influenced by the myelo-architecture of the stimulation site and the excitability of individual cortical neurones.