Selective cholinergic modulation of cortical GABAergic cell subtypes

Abstract

Acetylcholine from the basal forebrain and γ-aminobutyric acid (GABA) from intracortical inhibitory interneurons exert strong influence on the cortical activity and may interact with each other. Cholinergic or muscarinic agonists indeed induced GABAergic postsynaptic currents in pyramidal cells by exciting inhibitory interneurons that have recently been classified into several distinct subtypes on the basis of the physiological, chemical, and morphological criteria. Cholinergic effects on GABAergic cell subtypes were investigated of rat frontal cortex by in vitro whole cell recording with intracellular staining in frontal cortex of young rats. GABAergic cell subtypes were identified physiologically by firing responses to depolarizing current pulses and immunohistochemically as containing parvalbumin, somatostatin, vasoactive intestinal polypeptide (VIP), or cholecystokinin (CCK). Carbachol (10 μM) or (+)-muscarine (3 μM) affected the activities of peptide-containing GABAergic cells with regular- or burst-spiking characteristics, but not of GABAergic cells with fast-spiking characteristics containing the calcium-binding protein parvalbumin or GABAergic cells with late-spiking characteristics. Somatostatin-or VIP-immunoreactive cells were depolarized with spike firing. CCK-immunoreactive cells were affected heterogeneously by cholinergic agonists. Larger CCK cells were hyperpolarized, followed by a slow depolarization, whereas smaller CCK cells were only depolarized. These results suggest that the excitability of cortical GABAergic cell subtypes is differentially regulated by acetylcholine. Differences in cholinergic responses suggest a distinct functional role of each GABAergic cell subtype.