α1 Adrenergic receptor regulation of interneuron function

Abstract

Adrenergic receptors (ARs) have been shown to regulate neuronal function in diverse ways, from altering membrane potential and transmitter release to effects on gene expression. Activation of α1ARs produces a membrane depolarization in a specific subset of hippocampal interneurons. Evidence from transgenic mice either lacking (KO) or overexpressing (CAM) α1A or α1BARs suggests that the majority of this response is due to activation of α1AARs. Electrophysiological recordings during application of α1AR agonists produced a concentration‐dependent increase in action potential frequency in hippocampal interneurons from normal and α1BAR KO mice, but not α1AAR KO mice. α1AR agonists also increased the frequency and amplitude of IPSCs in CA1 pryamidal neurons. Mice overexpressing α1AARs showed increased hippocampal interneuron density. BrdU immunohistochemistry revealed enhanced neurogenesis in CAM α1AAR animals. This result was also observed in normal mice treated with the α1AAR agonist, cirazoline. Furthermore, when compared to controls, CAM α1AAR mice showed an increase in latency periods preceding seizures when exposed to the epileptogenic agent, flurothyl. These findings suggest that activation of α1AARs increases inhibitory tone not only via increased interneuron firing but possibly by increased numbers of interneurons. These findings are potentially very significant as they link α1AAR‐induced proliferation of interneurons to the antiepileptic actions of the adrenergic system. Supported by NIH R01HL61438, NIH COBRE, NSF ND EPSCoR, NSF CAREER, Epilepsy Foundation.