Firing dynamics of thalamic and cortical neural networks during absence epilepsy
Epilepsy is one of the most serious and widespread neurological diseases, which affect about 1% of the population.
Childhood absence epilepsy is characterized by a sudden and relatively brief impairment of consciousness, occurring concomitantly with a generalized and bilaterally synchronous ‘(poly)spike and slow wave discharge’ (SWD) paroxysm at 2.5-4 Hz in the EEG. These SWDs are known to be generated by abnormal firing in the thalamus and cortex, but a detailed picture of how the firing properties of these neurons lead to the absence phenotype is still lacking. Our recent technical achievements now allow us to record simultaneously from large cortical and thalamic neuronal populations during absence seizures in freely moving animal models of this disease. In particular, we are trying to answer the following questions: 1) are the majority of thalamic neurons silent during SWDs or do they show burst firing? 2) Do individual TC neurons of sensory thalamic nuclei switch from burst firing to a silent pattern during successive SWDs (as suggested by computer simulations), or do the bursting and silent neurons belong to two distinct neuronal pools? 3) which are the precise spatio-temporal firing dynamics of pyramidal and non-pyramidal in different cortical layers during SWDs? 5) Is the presence of thalamic paroxysmal activity required for the full manifestation of an absence seizure, i.e. concomitant expression of SWDs and its behavioural correlates (e.g. behavioural arrest, vibrissae twitching, head jerks, etc.)?
Outline of Techniques
Deep brain electrode implantation; simultaneous recording of electrical activity from large neuronal populations (>50 neurons) using state-of-the-art technology (i.e. silicone probes) in freely moving animals; implantation of microdialysis probes; localized application in discrete brain areas of neuroactive drugs, receptor antagonists and anti-epileptic drugs; auto- and cross-correlation analysis of firing activity, and sliding window cross-correlation.