Abstract
Infantile Spasms (IS) is one of the most severe and enigmatic of all the epileptic syndromes, and can be characterized by intractable seizures, a specific electroencephalogram (EEG) trace known as “hypsarrythmia”, and poor developmental outcome. However, the fundamental neurobiological mechanisms underlying epileptogenesis in the latency period before IS becomes observable, is currently being hampered by the lack of sufficient animal models to recreate the disorder. This study seeks to capture the full potential of the most promising model proposed, the TTX/activity deprivation model. Specifically, we want to use the model to investigate the idea of “acquired internueronopathy,” which implicates acquired interneuron dysfunction as the underlying pathogenesis for IS. To accomplish this, the TTX model was reformatted for use in a mouse, in order to utilize transgenic mice lines. Mice 13 days of age received 5 or 6 days of chronic TTX infusion at.25 μL/hr into the developing somatosensory cortex. Neuronal electrophysiological properties were assessed for neurons in the ipsi lateral hemisphere (around the infusion site) or in the contra lateral hemisphere for both TTX infused mice and ACSF (control) infused mice. The results of the intrinsic firing rate assay implied a negative effect of TTX; it had no effect on the excitabilities of parvalbumin positive interneurons. When we instead assessed the synaptic output of interneurons, we discovered a trending decrease in the frequency of inhibitory vesicles released in the contralateral hemisphere. However, the great potential of this model is the easy by which future electrophysiological and electroencephalographic assays can be performed in presymptomatic IS mice. These future experiments will help clarify exactly which neurological changes produce the IS phenotype.