Slow synchronized bursts of inhibitory postsynaptic currents (0.1-0.3 Hz) by cholinergic stimulation in the rat...

Cholinergic inputs from the basal forebrain to cortex exert profound effects on cortical activities, such as a rhythmic synchronization. For these modulatory effects inhibitory interneurons could play crucial roles within the cortical circuitry. To study cholinergic modulation of GABA-mediated inhibition, we recorded inhibitory postsynaptic current (IPSC) during application of cholinergic agonists in the rat frontal cortex in vitro. Both carbachol and muscarine caused two temporally different patterns of IPSC modulation in both pyramidal cells and inhibitory interneurons: tonic or periodic increase of GABA-A receptor-mediated inhibition. The tonic pattern showed a continuous increase of IPSC frequency, while the periodic increase manifested itself as rhythmic (0.1-0.3 Hz, mean 0.2 Hz) bursts of IPSC (frequency: 6-69 Hz, mean 24 Hz; burst duration: 1.2-4.3 s, mean 2.2 s). Both types of increase were suppressed by atropine or pirenzepine, muscarinic-receptor antagonists. The periodical IPSC bursts were not affected by antagonists for ionotropic glutamate receptors. Following cholinergic stimulation, periodic IPSC bursts in nearby cells were synchronized as a whole, but individual inhibitory events within the bursts were not always temporally correlated, suggesting synchronized depolarizations of several presynaptic interneurons. It has been revealed that slow rhythmic depolarizations accompanying spike firing can be generated within the cortex. In addition to this periodic excitation of cortical circuits, these results indicate that cortical inhibitory interneurons have their own acetylcholine-dependent mechanism generating the slow rhythm independent of the excitatory circuits.