Altered Noradrenergic Modulation of Dentate Granule Cell Firing and N-Methyl-D-Aspartate (NMDA) Receptors After Kindlung

Depleting brain norepinephrine (NE) impairs long-term potentiation (LTP) of perforant path (PP)-dentate gyrus (DG) synapses, promotes induction of kindled epilepsy, and NE elicits long-lasting potentiation of PP evoked potentials. We now report that NE enhances both stimulus and NMDA induced Ca2+ influx into granule cells via α1 receptors, and elicits long-lasting depolarization requiring NMDA receptor activation to persist. Furthermore, the induction of kindled epilepsy is associated with reduced sensitivity to NE, which may represent a neuronal “write-protect” mechanism and also contribute to epileptogenesis.