Excitatory actions of norepinephrine on multiple classes of hippocampal CA1 interneurons

Dwight E. Bergles, Van A. Doze, Daniel V. Madison, Stephen J. Smith

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


Norepinephrine (NE) causes an increase in the frequency of inhibitory postsynaptic potentials in CA1 pyramidal neurons in vitro. The possibility that this increase in tonic inhibition is caused by an excitatory effect on inhibitory interneurons was investigated through whole-cell recordings from pyramidal cells and both whole-cell and cell-attached patch recordings from visualized interneurons in acute slices of rat hippocampus, Adrenergic agonists caused a large increase in the frequency and amplitude of spontaneous IPSCs recorded from pyramidal cells in the presence of ionotropic glutamate receptor blockers, but they had no effect on either the frequency or the amplitude of action potential-independent miniature IPSCs recorded in tetrodotoxin. This effect was mediated primarily by an α adrenoceptor, although a slight β adrenoceptor-dependent increase in IPSCs was also observed. NE caused interneurons located in all strata to depolarize and begin firing action potentials. Many of these cells had axons that ramified throughout the stratum pyramidale, suggesting that they are responsible for the IPSCs observed in pyramidal neurons. This depolarization was also mediated by an α adrenoceptor and was blocked by a selective α1- but not a selective α2-adrenoceptor antagonist. However, a slight β adrenoceptor- dependent depolarization was detected in those interneurons that displayed time-dependent inward rectification. In the presence of a β antagonist, NE induced an inward current that reversed near the predicted K+ equilibrium potential and was not affected by changes in intracellular Cl concentration. In the presence of an α1 antagonist, NE induced an inwardly rectifying current at potentials negative to approximately -70 mV that did not reverse (between -130 and -60 mV), characteristics similar to the hyperpolarization- activated current (I(h)). However, the depolarizing action of NE is attributable primarily to the α1 adrenoceptor-mediated decrease in K+ conductance and not the β adrenoceptor-dependent increase in I(h). These results provide evidence that NE increases action potential-dependent IPSCs in pyramidal neurons by depolarizing surrounding inhibitory interneurons. This potent excitatory action of NE on multiple classes of hippocampal interneurons may contribute to the NE-induced decrease in the spontaneous activity of pyramidal neurons and the antiepileptic effects of NE observed in vivo.

Original languageEnglish (US)
Pages (from-to)572-585
Number of pages14
JournalJournal of Neuroscience
Issue number2
StatePublished - Jan 15 1996
Externally publishedYes


  • CA1
  • GABA
  • IPSC
  • epilepsy
  • hippocampus
  • interneuron
  • norepinephrine
  • α adrenoceptor

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Excitatory actions of norepinephrine on multiple classes of hippocampal CA1 interneurons'. Together they form a unique fingerprint.

Cite this