Altered intrinsic properties of neuronal subtypes in malformed epileptogenic cortex

Abstract

Neuronal intrinsic properties control action potential firing rates and serve to define particular neuronal subtypes. Changes in intrinsic properties have previously been shown to contribute to hyperexcitability in a number of epilepsy models. Here we examined whether a developmental insult producing the cortical malformation of microgyria altered the identity or firing properties of layer V pyramidal neurons and two interneuron subtypes. Trains of action potentials were elicited with a series of current injection steps during whole cell patch clamp recordings. Cells in malformed cortex identified as having an apical dendrite had firing patterns similar to control pyramidal neurons. The duration of the second action potential in the train was increased in paramicrogyral (PMG) pyramidal cells, suggesting that these cells may be in an immature state, as was previously found for layer II/III pyramidal neurons. Based on stereotypical firing patterns and other intrinsic properties, fast-spiking (FS) and low threshold-spiking (LTS) interneuron subpopulations were clearly identified in both control and malformed cortex. Most intrinsic properties measured in malformed cortex were unchanged, suggesting that subtype identity is maintained. However, LTS interneurons in lesioned cortex had increased maximum firing frequency, decreased initial afterhyperpolarization duration, and increased total adaptation ratio compared to control LTS cells. FS interneurons demonstrated decreased maximum firing frequencies in malformed cortex compared to control FS cells. These changes may increase the efficacy of LTS while decreasing the effectiveness of FS interneurons. These data indicate that differential alterations of individual neuronal subpopulations may endow them with specific characteristics that promote epileptogenesis.