Studies on Neuronal Excitability and Mechanism Underlying Epilepsy


Yousheng Shu, Ph.D. Principal Investigator Institute of Neuroscience, Chinese Academy of Sciences


2012.04.18 14:00-15:00


601 Pao Yue-Kong Library


In this talk, I will present our recent findings on: 1) The role of Na+ channel subtypes in controlling action potential (AP) initiation and backpropagation in cortical pyramidal neurons. The ability of firing APs determines the neuronal excitability. Early studies demonstrated that APs are normally initiated at the axon initial segment (AIS), presumably due to a high density of Na+ channels. However, we show that the low-threshold Nav1.6 channels that accumulate at the distal end of the AIS determine AP initiation, whereas the high-threshold Nav1.2 channels promote AP backpropagation into the soma and dendrites. 2) The role of membrane potential-mediated analog signaling in controlling the balance of excitation (E) and inhibition (I) in the cortex. We found that the amount and timing of recurrent inhibition is regulated by the membrane potential of presynaptic excitatory neurons. Depolarization (increased excitation) in pyramidal neurons can increase the peak amplitude of AP-triggered EPSPs in inhibitory neurons and thus increase the firing probability and AP numbers in these inhibitory neurons, leading to an enhancement of recurrent inhibition. Using this mechanism, the cortex is able to maintain the E-I balance and prevent hyperexcitability. 3) The changes in asynchronous release (AR) of GABA in the epileptic cortex. Down-regulation of GABA system contributes to epileptogenesis. However, we revealed an increase in AP burst-induced AR in either human or rat epileptic tissues, which may shape the epileptiform activities in the cortex.