Enhanced excitability of CA1 pyramidal neurons during the latent phase of the Rat lithium-pilocarpine model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a prevalent neurological disorder, with a significant proportion of cases remaining resistant to pharmacological treatment. Understanding the mechanisms underlying epileptogenesis-the process by which a normal brain becomes epileptic-is crucial for developing effective therapeutic strategies. In this study, we investigated changes in the intrinsic excitability of CA1 pyramidal neurons during the latent phase of the lithium-pilocarpine model of TLE, a period critical for the development of spontaneous recurrent seizures. Using whole-cell patch-clamp recordings, we analyzed firing patterns, passive membrane properties, and action potential dynamics in hippocampal slices from rats at 1, 3, and 7 days post-status epilepticus (SE). Our results demonstrate that CA1 neurons exhibit increased excitability during the latent phase, characterized by elevated maximal action potential frequency, reduced medium afterhyperpolarization (mAHP) timing, and transient changes in passive membrane properties such as depolarized resting membrane potential and increased input resistance. These changes were most pronounced on the 3rd day post-SE, coinciding with a critical period of epileptogenesis. Additionally, we observed a significant increase in the proportion of neurons exhibiting spike doublets, a phenomenon associated with enhanced excitability. These findings suggest that alterations in the intrinsic properties of CA1 neurons during the latent phase contribute to the hyperexcitability of hippocampal networks, potentially facilitating the transition to chronic epilepsy.