From Microscopic to Macroscopic – Mechanisms Underlying Epileptic Seizures

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Several laboratories, including my own, study synaptic and intrinsic function of neurons in multiple areas of the hippocampus, as these cellular properties are dysregulated by the development and expression of epilepsy. In two areas in particular, the dentate gyrus and area CA1, many laboratories have found significant changes in inhibitory synaptic function, which are predominantly expressed early in the development of epilepsy and in the chronic state, respectively. Extending these studies of synapses in single neurons, we have also begun voltage-sensitive dye imaging of the function of neuronal circuits within the hippocampus, with a goal of understanding how dysregulated synaptic function in individual cells alters the behavior of limbic circuitry. We have found that, accompanying the development of dyregulated activity in inhibitory synapses, both the dentate gyrus and area CA1 exhibit profound and distinct disruption of normal circuit properties. This combined micro- and medium-scale functional approach provides unique levels of insight into epileptogenic mechanisms.