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Old age is the most common time for patients to develop epileptic seizures, and due to their frequent unusual clinical presentation the diagnosis of epilepsy is often delayed in the elderly. It is as yet unknown if pronounced alterations in the plastic properties of aging nervous tissue contribute to these phenomena. We employed a non-lesional in vitro epilepsy model to study seizure susceptibility, spread pattern, and propagation velocities in combined hippocampal-entorhinal cortex slices of aged rats and controls using electrophysiological methods and imaging of intrinsic optical signals. In aged animals we saw a less extensive spread of seizure-like events into areas adjacent to the region of onset of activity and a decreased spread velocity in various anatomical regions. In addition, both the activity-dependent shrinkage of the extracellular space (ECS)-volume and the extracellular K(+) concentration were significantly reduced compared to controls. The results of this study are consistent with the clinical observation that epileptic seizures in the elderly have a reduced tendency to spread. In addition, our data suggest that in the absence of structural lesions seizure susceptibility in the aging brain is not increased.

Recent evidence suggests that electrotonic coupling is an important mechanism for neuronal synchronisation in the mammalian cortex and hippocampus. Various types of network oscillations have been shown to depend on, or be sharpened by, gap junctions between inhibitory interneurones or excitatory projection cells. Here we made use of a targeted disruption of the gene coding for Cx36, a recently discovered neuronal gap junction subunit, to analyse its role in hippocampal network behaviour. Mice lacking Cx36 are viable and lack obvious morphological or behavioural abnormalities. Stimulation of afferent and efferent fibre pathways in hippocampal slices revealed a largely normal function of the synaptic circuitry, including tetanically evoked network oscillations. Spontaneous sharp waves and ripple (approximately 200 Hz) oscillations, however, occurred less frequently in slices from Cx36 -/- mice, and ripples were slightly slower than in littermate controls. Moreover, epileptiform discharges elicited by 4-aminopyridine were attenuated in slices from Cx36 -/- mice. Our findings indicate that Cx36 plays a role in the generation of certain forms of network synchronisation in the hippocampus, namely sharp wave-ripple complexes and hypersynchronous epileptiform discharges.