Abstracts

Rationale: Multiple epilepsies and seizure disorders are treated by pharmacologically increased GABAergic tone. Following successful control of the seizures with anti-epileptic drugs (AEDs), new cognitive side effects appear or previous deficits are not remediated. A main question in epilepsy is the cause of the impaired learning, the general lack of inhibition and/or the innate neural circuitry. Methods: Neural recordings were obtained from awake transgenic mice with specific deficits in frontal lobe interneurons while performing cognitive tasks. Electrode arrays recorded single unit and local field potential activity during correct and incorrect trials and during the intertrial intervals. The local field potential activity was used as the surrogate for the EEG. Results: Control mice demonstrated low baseline activity and increased signal in the delta range upon correct choices. In agreement with previous studies, the control mice made few errors and readily learned the tasks. Mice with decreased parvalbumin interneurons had difficulty learning the task, demonstrating increased numbers of errors. In absence of parvalbumin cells, the baseline of the local field potential showed increased power in the alpha range and overall increased amplitude. The signal:noise ratio in the mice with parvalbumin deficits was greatly reduced. Conclusions: In addition to providing inhibition to stabilize the neural network and prevent seizure activity, parvalbumin interneurons assist in coding information required for proper learning. Perturbations in the neural network away from the optimum impaired cognition.