Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy

Abstract

The subiculum was recently shown to be crucially involved in the generation of interictal activity in human temporal lobe epilepsy. Using the pilocarpine model of epilepsy, this study examines the anatomical substrates for network hyperexcitability recorded in the subiculum. Regular- and burst-spiking subicular pyramidal cells were stained with fluorescence dyes and reconstructed to analyze seizure-induced alterations of the dendritic and axonal system. In control animals burst-spiking cells outnumbered regular-spiking cells by about two to one. Regular- and burst-spiking cells were characterized by extensive axonal branching and autapse-like contacts, suggesting a high intrinsic connectivity. In addition, subicular axons projecting to CA1 indicate a CA1-subiculum-CA1 circuit. In the subiculum of pilocarpine-treated rats we found an enhanced network excitability characterized by spontaneous rhythmic activity, polysynaptic responses, and all-or-none evoked bursts of action potentials. In pilocarpine-treated rats the subiculum showed cell loss of about 30%. The ratio of regular- and burst-spiking cells was practically inverse as compared to control preparations. A reduced arborization and spine density in the proximal part of the apical dendrites suggests a partial deafferentiation from CA1. In pilocarpine-treated rats no increased axonal outgrowth of pyramidal cells was observed. Hence, axonal sprouting of subicular pyramidal cells is not mandatory for the development of the pathological events. We suggest that pilocarpine-induced seizures cause an unmasking or strengthening of synaptic contacts within the recurrent subicular network.

In vitro ictogenesis and parahippocampal networks in a rodent model of temporal lobe epilepsy

“…The involvement of the subiculum in epileptiform synchronization is also evidenced by the ability of this region to generate spontaneous rhythmic discharges in human epileptic tissue (Cohen et al, 2002;Wozny et al, 2005b) even when not stricken by hippocampal sclerosis (Wozny et al, 2005b), suggesting that both synaptic and intrinsic neuronal alterations underlie the increased seizure susceptibility of this region. In line with these results, pyramidal neurons exhibit hyperexcitability in the epileptic rat subiculum (Knopp et al, 2005;de Guzman et al, 2006), where, similarly to what was reported from human brain specimens (Huberfeld et al, 2007) downregulation of the K + /Cl − cotransporter KCC2 accounts for a depolarized reversal potential of GABA A -mediated IPSPs (de Guzman et al, 2006). In addition, we have reported that subicular expression of FosB/ΔFosB is increased after pilocarpine-induced SE (Biagini et al, 2005), suggesting robust activation of this region during seizure activity.…”

“…The latter changes along with NMDA receptor upregulation have been reported in pilocarpine-treated parahippocampal areas such as the subiculum (Knopp et al, 2005;de Guzman et al, 2006), the EC (Kobayashi et al, 2003;Kumar and Buckmaster, 2006;Yang et al, 2006;de Guzman et al, 2008) and the lateral amygdala (LA) (Benini and Avoli, 2005). In addition, modified GABA A receptor signaling due to changes in K + /Cl − cotransporter has been identified in the epileptic human subiculum in vitro (Cohen et al, 2002;Wozny et al, 2003;Huberfeld et al, 2007).…”

High-frequency (80–500Hz) oscillations and epileptogenesis in temporal lobe epilepsy

“…Several in vitro studies have demonstrated that the subiculum plays a pivotal role in the pilocarpine model of temporal lobe epilepsy, and in the human condition (de Guzman et al, 2006;Knopp et al, 2005;Vreugdenhil et al, 2004;Wellmer et al, 2002). Ex vivo experiments have also shown increased expression of FosB/ΔFosB in the subiculum of pilocarpine-treated rats (Biagini et al, 2005).…”

Activity-Dependent Depression of Local Excitatory Connections in the CA1 Region of Mouse Hippocampus

“…2B). This indicates that the polysynaptic EPSPs recorded in our experiments are not due to synaptic inputs onto CA1 pyramidal cells arising from the subiculum (Berger et al 1980;Commins et al 2002;Harris et al 2001;Knopp et al 2005) but are instead due to local excitatory connections between CA1 pyramidal cells. Moreover, activation of 5-HT 1B receptors with CP93129 (10 M), which selectively inhibits local excitatory synapses between CA1 pyramidal cells (Mlinar et al 2001(Mlinar et al , 2003, strongly suppressed polysynaptic EPSPs elicited by Schaffer collateral fiber stimulation (Fig.…”