Abstracts

Rationale: The origin of seizures continues to remain a mystery, despite many decades of investigation. The various parameters involved in ictogenesis are often not easy to evaluate experimentally. In our work, we create a computational model of the CA3 region of the hippocampus. We then proceed to evaluate how variation of different parameters influences the generation and characteristics of seizures.Methods: Our model has a layer of 100 x 100 pyramidal cells, interspersed with a 15 x 15 array of interneurons. We use the MacGregor model for our neurons. Every neuron is connected to a neighborhood of surrounding neurons, using several different strategies for synaptic connectivity. Synapses were designed to undergo activity-dependent short-term depression and recovery. The initial number of releasable glutamate vesicles in each presynaptic terminal was normally distributed. The amount of glutamate released at a synapse depends on: 1) probability of release of a glutamate vesicle and 2) the number of releasable glutamate vesicles currently available at the synapse. Both spontaneous release and activity dependent release of glutamate are supported by the model. We also model release of GABA at inhibitory synapses. In this work, we are investigating 1) the role that synaptic connectivity strategies play in seizure threshold 2) how the initial distribution of releasable glutamate may play a role in the transition from bursting to ictal like activity. 3) how variation in release of GABA may play a role in generation of ictal like activity.Results: Our initial findings were that a critical level of variance in the availability of releasable glutamate was ictogenic. We are currently completely rebuilding the network in order to replicate this work and ascertain the robustness of our startling initial results. We are also ascertaining the role played by variation in GABA release in ictogenesis.Conclusions: In our work, a computational model of the CA3 region of the hippocampus was created and the various parameters that influence the generation of seizures were evaluated. The parameters we focus are glutamate, and its distribution, GABA, and models of synpatic connectivity.