α2A Adrenergic Receptors Modulate CA3‐CA3 Pyramidal Cell Communication in the Rat Hippocampus

Abstract

The adrenergic system has potent antiepileptic properties and also enhances certain memory processes. The pharmacology and mechanisms underlying these remain unclear. We have identified an α2A adrenergic receptor (α2AAR) which robustly inhibits the initiation of epileptiform activity in the CA3 region of the rat hippocampus, a structure critical for learning and memory and also a common focus for temporal lobe seizures. Using whole‐cell recordings, we examined excitatory post‐synaptic currents evoked from the major CA3 synaptic inputs (mossy fiber and CA3 recurrent), as well as the CA3 inputs onto CA1 pyramidal neurons to further localize this adrenergic effect. Electrophysiological evidence suggests that α2A‐AR activation preferentially inhibits the recurrent hippocampal CA3 glutamatergic synapses compared to the excitatory drive to and from the CA3 cells. Further electrophysiological evidence suggests that this occurs though a presynaptic inhibition of glutamate release. Since overexcitation of the recurrent CA3 synapses is thought to occur in temporal lobe seizures, selective inhibition of presynaptic hippocampal excitatory communication may explain how the adrenergic system may be antiepileptic while at the same time not affect other cognitive functions such as learning or memory. This study was supported in part by the Epilepsy Foundation (CWDJ), North Dakota EPSCoR through NSF grant EPS‐0447679 (VAD), NSF CAREER award 0347259 (VAD), and NIH grant 5P20RR017699 from the COBRE program (VAD).