Noradrenergic Excitation and Inhibition of GABAergic Cell Types in Rat Frontal Cortex

Abstract

Noradrenaline (NA) from the locus coeruleus and GABA from intracortical nonpyramidal cells exert strong influences on cortical activity. To assess possible interaction between the two, the effects of noradrenergic agonists on spontaneous GABAergic IPSCs as well as on the activity of identified GABAergic cell types were investigated by in vitro whole-cell recordings from the frontal cortex of 18- to 22-d-old rats. NA (3-50 microM) and an alpha-adrenergic agonist, 6-fluoronorepinephrine (FNE; 30-50 microM), induced an increase of IPSC frequency in pyramidal cells, but a beta-adrenergic agonist did not. This increase was reduced by tetrodotoxin, bicuculline, and alpha-adrenergic antagonists, suggesting that GABAergic cells are excited via alpha-adrenoceptors. Fast-spiking or late-spiking cells were depolarized by application of NA or FNE, but none demonstrated spike firings. The former morphologically included common multipolar cells with extended axonal arborizations as well as chandelier cells, and the latter neurogliaform cells. Most somatostatin-immunoreactive regular or burst-spiking cells, including Martinotti cells and wide arbor cells, were depolarized and accompanied by spike firing. In a few cases this was preceded by hyperpolarization. Cholecystokinin-immunoreactive regular or burst-spiking nonpyramidal cells, including large basket cells, were affected heterogeneously: depolarization, hyperpolarization followed by depolarization, or hyperpolarization resulted. The findings suggest that, similar to the effects of acetylcholine, the excitability of cortical GABAergic cell types is differentially regulated by NA and that NA actions are similar to cholinergic ones in some GABAergic cell types but not in others.