Abstracts

Neurogenesis continues in the adult mammalian brain from neural stem/progenitor cells in the dentate gyrus subgranular zone (SGZ). Status epilepticus (SE) triggers increased SGZ cell proliferation. Intracellular recordings from the aberrant hilar neurons in hippocampal slices from epileptic rats indicate that they retain the intrinsic properties of granule cells. However, they exhibit abnormal pro-epileptogenic burst firing in synchrony with CA3 pyramidal cells, suggesting that the new hilar neurons contribute to the epileptic condition. The functional characteristics of the majority of the new cells generated in the epileptic brain, which are located at their normal site in the granule cell layer, have not been investigated., We have used whole-cell patch-clamp recordings to determine how a pathological environment influences the electrophysiological properties and functional integration of the new cells in the GCL. New neurons were labeled through intrahippocampal injection of RV-GFP and we compared those generated following voluntary running, i.e., a physiological stimulus, with cells formed after SE, i.e., a brain insult., We found that the new cells differentiate into functionally integrated granule cells with similar intrinsic membrane properties in both running and SE environments. However, the neurons born in the epileptic brain show alterations in excitatory and inhibitory inputs, which could attenuate synaptic excitability: The excitatory synaptic drive was attenuated on the new cells born into the epileptic environment compared to those formed under physiological conditions, while the inhibitory synaptic drive on these cells was increased., Our study demonstrates that both a physiological stimulus and an insult to the adult brain trigger the formation of new dentate granule cells, which are functionally integrated into hippocampal neural circuitry. However, following the insult, the functional connectivity of the new neurons seems to mitigate the dysfunction in the epileptic brain. These data provide further evidence for a therapeutic potential of endogenous neurogenesis., (Supported by Swedish Research Council, and Segerfalk, Crafoord and Kock foundations.)