Acceleration of pentylenetetrazol seizure kindling associated with induction of sensitized visual responses evoked by strobe stimulation

Abstract Exposure of normal adult rats of a variety of species to trains of light flashes leads to acquisition of an enduring high amplitude visual cortical response [Uhlrich DJ, Manning KA, O'Laughlin ML, Lytton WW (2005) Photic-induced sensitization: acquisition of an augmenting spike-wave response in the adult rat through repeated strobe exposure. J Neurophysiol 94:3925–3937]. The photically-induced sensitized response exhibits epileptiform characteristics, including spike-wave morphology, tendency to generalize across the brain, and sensitivity to the anti-epileptic drug ethosuximide. These findings and anecdotal clinical reports raise the possibility that certain sensory stimulation could induce neural plastic changes that affect seizures in some individuals. We hypothesize that photic-induced sensitization can prime seizure-related neural circuitry, resulting in exacerbation of seizures. To test this we compared seizure kindling rates using the pentylenetetrazol (PTZ) model of epileptogenesis in sensitized and unsensitized adult Sprague–Dawley rats. Experimental group rats were sensitized by exposure to repetitive stroboscopic stimulation over 4–6 days until the sensitized photic response fully developed and response magnitude stabilized at its highest plateau. Rats then received a sub-convulsive injection of PTZ (24 mg/kg i.p.) every other day until they attained class 5 seizures. Control rats were not strobed or sensitized, but were otherwise treated identically. Chronic electrodes overlying the dura in occipital cortex recorded the primary visual response. Similar electrodes near the border of somatosensory and motor cortex (SM) were used to record spread of the sensitized response to a patently non-visual region. Rat behavior was monitored by direct observation and digital audio/video recording. All control rats and seven of 14 photically sensitized rats kindled seizures at rates consistent with those reported previously. However, the seven other photically sensitized rats displayed markedly accelerated seizure kindling. Rats with accelerated kindling showed greater spread of the sensitized visual response to somato-motor cortex and, when tested in a post hoc experiment, exhibited a higher likelihood of photo-triggered seizures. These results indicate that photic-induced sensitization in susceptible individuals can prime neural circuitry involved in the generation of PTZ-kindled seizures.