Effects of Neuropeptide Y on Single Neuronal Firing Patterns in a Genetic Rat Model of Absence Epilepsy

Effects of neuropeptide y on single neuronal firing patterns in a genetic rat model of absence epilepsy Date: Effects of neuropeptide y on single neuronal firing patterns in a genetic rat model of absence epilepsy 1 ABSTRACT Absence seizures are most common type of generalized seizures where brain goes into abnormal pathological rhythm characterized by bilateral and synchronous 3Hz spike and wave discharges on EEG. Currently available anti-epileptic drugs do not have adequate seizure control and have adverse side effects, which increased the desire for development of novel therapeutic options for treating absence seizures. Previous studies demonstrated that neuropeptide Y (NPY) successfully suppresses absence seizures in genetic rat model of absence epilepsy but the underlying neuronal mechanisms for seizure suppression still remain unknown. Recent developments in electrophysiology enabled the quantification of neuronal firing patterns in vivo and many researchers have already demonstrated differential characteristic firing patterns of neurons in thalamo cortical circuit in the brain that plays a critical role in absence seizures. This study was designed to investigate the effects of intracerebroventricular (ICV) and locally administered NPY on neuronal firing patterns in thalamocortical structures, which play a critical role in the generation of absence like seizures in GAERS as well as effects on seizure induction threshold in the cortical S2 region. Methods All experiments were conducted on 8-12 weeks old male GAERS rats. This involved performing in vivo electrophysiological recordings under neurolept anaesthesia. In these experiments single neuronal firing activity was recorded from different regions of thalamocortical circuit. Once stable electrophysiological recordings are achieved, NPY was infused both ICV and focally at the recording site and alterations in the neuronal firing patterns were assessed before and after the drug intervention. In another experiment cortical region S2 was stimulated by external electrical stimulation to induce absence 4 like seizure and effects of ICV administration of NPY on seizure triggering threshold in the S2 region was assessed in GAERS. Results NPY suppressed absence seizures in GAERS by reducing total seizure length and percentage of time spent in seizures under neurolept analgesia. In addition, we also demonstrate that NPY mediated reductions in the seizure levels (absence) were associated with increased firing frequency of the NRT neurons interictally in these rats. ICV and focal administration of NPY increased the mean firing frequency of the NRT neurons in interictal periods. Control experiments were performed with saline injections .The saline infusion data showed no change …