Focal administration of neuropeptide Y into the S2 somatosensory cortex maximally suppresses absence seizures in a genetic rat model

Purpose: Neuropeptide Y (NPY) is an inhibitory neurotransmitter that suppresses focal and generalized seizures in animal models. In this study, we investigated the sites within the thalamocortical circuit that NPY acts to suppress seizures in genetic absence epilepsy rats from Strasbourg (GAERS). Methods: In conscious freely moving GAERS, NPY was administered via intracerebral microcannulae implanted bilaterally into one of the following regions: primary somatosensory cortex (S1), secondary somatosensory cortex (S2), the primary motor cortex (M1), caudal nucleus reticular thalamus (nRT), or ventrobasal thalamus (VB). Animals received vehicle and up to three doses of NPY, in a randomized order. Electroencephalography (EEG) recordings were carried out for 30 min prior to injection and 90 min after the injection of NPY or vehicle. Key Findings: Focal microinjections of NPY into the S2 cortex suppressed seizures in a dose-dependent manner, with the response being significantly different at the highest dose (1.5 mM) compared to vehicle for total time in seizures postinjection (7.2 +/- 3.0% of saline, p < 0.01) and average number of seizures (9.4 +/- 4.9% of saline, p < 0.05). In contrast NPY microinjections into the VB resulted in an aggravation of seizures. Significance: NPY produces contrasting effects on absence-like seizures in GAERS depending on the site of injection within the thalamocortical circuit. The S2 is the site at which NPY most potently acts to suppress absence-like seizures in GAERS, whereas seizure-aggravating effects are seen in the VB. These results provide further evidence to support the proposition that these electroclinically "generalized'' seizures are being driven by a topographically restricted region within the somatosensory cortex.