Effects of topical application of diphenylhydantoin on gross evoked responses and single-neuron activity in pericruciate and precoronal cerebral cortex of the domestic cat

Abstract

Surface gross potentials and extracellular single-neuron responses evoked by stimulation of each of the four paws were recorded in the forepaw region of precoronal (field 3b), postcruciate, and precruciate (both field 4γ) tissues before and after topical application of diphenylhydantoin (DPH) to the surface recording site. When applied in crystalline form in any but the most minute amount, spreading cortical depression was induced. When applied in saline solution at 1 to 2 mg/ml, the primary gross response evoked by contralateral forepaw stimulation was markedly enhanced at the site of application, whatever the site. Occasionally, the primary response amplitude was briefly reduced, but it recovered within 2 min and then became enhanced for 15 to 90 min. By analogy with the “strychnine spike,” this greatly enhanced response is termed a “DPH spike.” At both pericruciate sites, DPH spikes developed from the small surface responses evoked by stimulation of the “off-focus” paws (ipsilateral forepaw and the two hind paws), as well as from the primary response evoked by contralateral forepaw stimulation. Single-neuron responsiveness to contralateral forepaw stimulation increased gradually as the DPH spike increased, and decreased as it decreased. Some neurons became responsive to off-focus paw stimulation when off-focus DPH spikes appeared. At the precoronal site, no off-focus DPH spikes appeared and no off-focus responsiveness developed on single neurons. In a few instances, an increase in the number of unit spikes per discharge occurred only during the first few responses to a 1 s iterative stimulus train, the responses returning to the pretreatment condition for the remainder of the stimulus train. Reinstituting the 1 s stimulus train after 5 to 10 min rest produced a similar transient enhancement of the neuron response. Thus, at a critical local concentration, this clinically anticonvulsant drug enhances the responsiveness of cerebral cortex to afferent input. Except for the transient enhancement of responsiveness seen on a few neurons, the effect is similar to, but weaker than, that produced by topical strychnine or bicuculline.