Abstracts

Rationale: Epilepsy is a common neurological disorder characterized by recurrent, unprovoked seizures, which are defined as a transient occurrence of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Abnormally synchronous brain activity may result in comorbidity of epilepsy with a number of psychosis syndromes. However, the pathophysiology of psychosis and its linkage to epilepsy remains obscure. We hypothesized a failure of neural coordination within and between specific networks of neurons as a pathophysiological mechanism that associates epilepsy and psychosis. We have begun to test this ‘discoordination’ hypothesis, initially by looking for signs of epilepsy in an animal model with well-established features of psychosis. Methods: The excitotoxin ibotenic acid (IBO; 10 mg/ml) or saline was injected bilaterally near the ventral hippocampus of male Long-Evans rats on postnatal day 7 (PD7). Local field potential (LFP) recordings (0.1-500 Hz) were performed when the rats were adult (PD>56). Rats were implanted with 75-µm electrodes in up to 16 sites for digital video-synchronized recordings. Recording targets included the piriform cortex, amygdala, entorhinal cortex, thalamus, medial prefrontal cortex, dorsal and ventral hippocampus. Skull-screws were used for epidural cortical recordings. Head-mounted amplifiers minimized noise and artifact. Results: IBO-treated rats (IBO rats) were compared to their saline-treated littermates (SAL rats). IBO rats exhibited sporadic, spontaneous, recurrent behavioral and electrographic seizures, and abnormalities that have not previously been reported in an animal model exhibiting features of psychosis. Initial analysis of the cortical recordings quantified 1-s electrographic events as normal or abnormal based on the distance of an event’s features from a distribution of normal event features. Abnormal events were far more likely in IBO rats (~30%) than SAL rats (~7%). A major component (~55%) of the abnormal events in IBO rats were spike-wave discharges occurring at ~5 Hz. Conclusions: As predicted by the discoordination hypothesis, that failures of neural coordination underlie cognitive impairments, abnormal epileptiform neural synchrony is a prominent electrographic characteristic of an animal model with schizophrenia-related behavioral and cognitive features.