Abstracts

Rationale: We seek to understand and control the conditions that lead to seizure initiation by performing an analysis within a system-theoretical framework, which is steered by observations in an experimental model of chronic epilepsy. Methods: We simulate the hippocampal CA3 region as a network of integrate-and-fire neurons with an anatomical synaptic topology that is modulated by use-dependent synaptic depression and recovery. The network exhibits high-dimensional, third-order nonlinear dynamics. The cornerstone of the modeling approach is short-term synaptic plasticity, that is, the modification in transmitter release probability, a process demonstrated experimentally to exhibit first-order depression and recovery kinetics. This type of synaptic plasticity may also underlie elements of activity-dependent disinhibition arising from depression of excitatory glutamatergic inputs to interneurons.  Results: Preliminary results are presented with respect to parameters that are within experimentally described ranges and that generate both stable interictal network activity and occasional ictal transitions. Conclusions: Keeping pace with experimental observations, this work exploits the rigor of dynamical systems theory towards unraveling the mechanisms of seizure onset. Funding: NIH