Monday July 3, 200612:00–13:30Hall 3DPlatform SessionBasic Science I: Molecules and Networks for Epileptogenesis

¹ M. Kokaia (   ¹ Wallenberg Neuroscience Center, Lund University Hospital, Sweden )
Purpose: Neural stem cells in the adult mammalian brain (including humans) continue to produce new functional granule cells in the dentate gyrus subgranular zone and new olfactory bulb neurons in the subventricular zone during an entire life. In the hippocampus, neurogenesis has been proposed to play a role in learning and memory and mood regulation. The new cells develop electrophysiological characteristics and synaptic inputs very similar to those of the rest of the cell population. The purpose of the study was to explore whether tissue environment in an epileptic brain influences properties of afferent synapses formed on newborn granule cells.
Method: Rats were exposed to either a physiological stimulus, i.e., running, or status epilepticus, which gives rise to neuronal death, inflammation, increased network excitability and recurrent spontaneous seizures. Both treatments increase neurogenesis in the dentate gyrus. We labelled newborn cells by GFP-retroviral vector injections right after these treatments to identify the cells and apply whole-cell patch-clamp recordings in live hippocampal slices.
Results: Granule cells formed after running and status epilepticus exhibited similar intrinsic membrane properties. However, new neurons born into the epileptic environment differed with respect to tonic drive and short-term plasticity of both excitatory and inhibitory afferent synapses. The new granule cells formed after status epilepticus exhibited functional connectivity consistent with reduced synaptic network excitability of the dentate gyrus, i.e., decreased excitatory and increased inhibitory input activity.
Conclusion: We demonstrate for the first time a high degree of plasticity in synaptic inputs to the new neurons, which could mitigate pathological activity in the epileptic brain.