Circadian rhythms mark the behavior of living beings across the day, primarily depending on light and darkness cycle and internal cellular clocks that act as the organism’s devices for regulating the timing of internal processes. These biological clocks are found in most tissues and organs included the brain where the master clock resides. At cerebral level, small changes due to internal clocks in protein expression are able to change neuron excitability. Epilepsy is a chronic disease of the central nervous system, affecting > 1% of the population, that manifest in the form of seizures. Within different types of epilepsy, temporal lobe epilepsy (TLE) is the most common form of focal epilepsy accounting for approximately 60% of all people living with epilepsy. In approximately 30% of epileptic patients, anti-epileptic drugs fail to control seizures. Moreover, the cause of many epileptic diseases is unknown in an estimated 60% of patients and no current treatment options are disease-modifying or are known to prevent epilepsy in these at-risk patients. Interestingly, the prevalence of seizures in TLE patients is higher during day period. This observation suggests an endogenous circadian control in temporal lobe excitability that is supported by our preliminary data. We propose to identify the changes controlled by internal clocks that regulate cellular excitability to provide novel therapeutic targets and treatment regimes to avoid seizure activity.
