Long‐lasting increased excitability differs in dentate gyrus vs. CA1 in freely moving chronic epileptic rats after electrically induced status epilepticus

Abstract

A paired-pulse (PP) stimulation protocol was used to examine changes in field potentials (fEPSPs), locally evoked in CA1 via Schaffer/ commissural fiber stimulation and in the dentate gyrus (DG) through angular bundle stimulation, in freely moving epileptic rats. This epilepsy model is characterized by recurrent spontaneous seizures that occur after a latent period of 1-2 weeks following an electrically induced status epilepticus (SE). In the control period, i.e., before induction of SE, the PP stimulation protocol given at the appropriate intensity evoked fEPSPs with a pronounced paired-pulse depression (PPD). In the acute period, immediately after SE, the fEPSPs in the CA1 and DG areas were generally depressed. During the latent period in the CA1 stratum radiatum, the negative fEPSP was followed by a large positive potential that remained for the rest of the recording period. CA1 PPD, observed during the control period, was changed to paired-pulse facilitation (PPF) that remained for the rest of the recording period. Also during the latent period, a broad late component appeared in DG fEPSPs. The initial decrease in PPD was partly restored in the following weeks. Timm staining at different time points after SE showed an increase of mossy-fiber sprouting in the inner molecular layer within 6 days, which was robust within 6 weeks. We noted Timm granules positioned on parvalbumin immunoreactive neurons in the granule-cell layer of rats that had survived SE, suggesting that restoration of PPD could be partly due to reinnervation of a population of GABAergic neurons. The broad late component of DG fEPSPs, which was sensitive to the NMDA receptor antagonist ketamine, was still present for at least 6 weeks into the chronic epileptic phase, indicating lasting increased excitability. These observed changes indicate a lasting increased excitability in CA1 and DG networks that could play a role in the recurrence of spontaneous seizures.

Abnormal neuronal patterning occurs during early postnatal brain development of Scn1b -null mice and precedes hyperexcitability

“…Functional loss of SCN1B also results in DS (9), showing that it is critical in regulating neuronal excitability, although the involvement of inhibitory neuronal circuitry in this process is unclear. Reduced PPD and increased PPF are often associated with loss or reduction of GABAergic inhibition (27)(28)(29). Thus, the enhanced PPF responses shown here (Fig.…”

Seizures, enhanced excitation, and increased vesicle number in Lis1 mutant mice

“…Indeed, while some postepileptic animals show a reduction in PPF, enhancement has been reported during the "latent period" in at least two rodent TLE models. 36,37 Interestingly, under conditions where presynaptic calcium channels are blocked (eg, a low concentration of cadmium), PPF was restored to normal levels, suggesting a potential new therapeutic mechanism. In one example of how this "therapy" could work, Glasscock et al showed that crossing a mutant mouse with a partial loss-of-function in a P/Q calcium channel subunit mediating transmitter release (Cacna1a Ϫ/Ϫ ) with an epileptic mouse (Kv1.1…”

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

“…Conversely, abnormally increased granule cell inhibition is consistently found during the chronic epileptic state (Sloviter, 1992;Buckmaster and Dudek, 1997;Wu and Leung, 2001;Gorter et al, 2002;Harvey and Sloviter, 2005). In contrast with the in vivo studies cited above, most in vitro studies have focused on the pathophysiological features of hippocampal slices revealed by incubation of slices in bicuculline (Cronin et al, 1992;Wuarin and Dudek, 1996;Molnar and Nadler, 1999) or elevated potassium (Patrylo and Dudek, 1998;Hardison et al, 2000).…”