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The CDC estimates one percent of adults in the United States have epilepsy. Temporal Lobe Epilepsy (TLE), which affects the hippocampus and surrounding cortices, is the most common form of focal epilepsy. Hypersynchronous seizure activity increases the likelihood of future seizures and causes progressive brain damage. In animal models of TLE, CA1 neurons have been shown to be susceptible to selective changes in ion channel expression, called acquired channelopathies, which increase the excitability of a neuron. In addition, several recent studies in normal rodents find differences in ion channel expression along the dorsoventral axis of CA1. It is unknown if the presence of acquired channelopathies depends on the dorsoventral region of CA1. Here, we show the excitability of dorsal and ventral CA1 neurons becomes uniform in a status epilepticus (SE) model of Temporal Lobe Epilepsy. Dorsal CA1 neurons post-SE have an increased firing rate, reduced interspike interval and increased input resistance, while the properties of ventral CA1 neurons remain stable post-SE. Potential mechanisms for these changes include a dysregulation in M, GIRK or HCN channels, which all have dorsoventral expression gradients and an existing link to epilepsy. Current clamp recordings with pharmacology and immunohistochemistry demonstrate the expression of M and GIRK channels do not change across the dorsoventral axis of CA1 post-SE. The expression of HCN channels, however, is downregulated in dorsal CA1 neurons post-SE contributing to the increased excitability of these neurons. This acquired channelopathy is not present in ventral CA1 neurons post-SE. These results suggest the excitability of dorsal CA1 neurons post-SE become more like ventral CA1 neurons, which likely makes the hippocampal circuit more permissible to seizures, and contributes to the cognitive impairments associated with chronic epilepsy.

The CDC estimates one percent of adults in the United States have epilepsy. Temporal Lobe Epilepsy (TLE), which affects the hippocampus and surrounding cortices, is the most common form of focal epilepsy. Hypersynchronous seizure activity increases the likelihood of future seizures and causes progressive brain damage. In animal models of TLE, CA1 neurons have been shown to be susceptible to selective changes in ion channel expression, called acquired channelopathies, which increase the excitability of a neuron. In addition, several recent studies in normal rodents find differences in ion channel expression along the dorsoventral axis of CA1. It is unknown if the presence of acquired channelopathies depends on the dorsoventral region of CA1. Here, we show the excitability of dorsal and ventral CA1 neurons becomes uniform in a status epilepticus (SE) model of Temporal Lobe Epilepsy. Dorsal CA1 neurons post-SE have an increased firing rate, reduced interspike interval and increased input resistance, while the properties of ventral CA1 neurons remain stable post-SE. Potential mechanisms for these changes include a dysregulation in M, GIRK or HCN channels, which all have dorsoventral expression gradients and an existing link to epilepsy. Current clamp recordings with pharmacology and immunohistochemistry demonstrate the expression of M and GIRK channels do not change across the dorsoventral axis of CA1 post-SE. The expression of HCN channels, however, is downregulated in dorsal CA1 neurons post-SE contributing to the increased excitability of these neurons. This acquired channelopathy is not present in ventral CA1 neurons post-SE. These results suggest the excitability of dorsal CA1 neurons post-SE become more like ventral CA1 neurons, which likely makes the hippocampal circuit more permissible to seizures, and contributes to the cognitive impairments associated with chronic epilepsy.