Network and intrinsic contributions to carbachol-induced oscillations in the rat subiculum

Low-frequency network oscillations occur in several areas of the limbic sys tem where they contribute to synaptic plasticity and mnemonic functions tha t are in turn modulated by cholinergic mechanisms. Here we used slices of t he rat subiculum (a limbic area involved in cognitive functions) to establi sh how network and single neuron (intrinsic) membrane mechanisms participat e to the rhythmic oscillations elicited by the cholinergic agent carbachol (CCh, 50-100 muM). We have found that CCh-induced network oscillations (int raoscillatory frequency = 5-16 Hz) are abolished by an antagonist of non-N- methyl-D-aspartate (NMDA) glutamatergic receptors (n = 6 slices) but persis t during blockade of GABA receptors (n = 16). In addition, during applicati on of glutamate and GABA receptor antagonists, single subicular cells gener ate burst oscillations at 2.1-6.8 Hz when depolarized with steady current i njection. These intrinsic burst oscillations disappear during application o f a Ca2+ channel blocker (n = 6 cells), intracellular Ca2+ chelation (n = 6 ), or replacement of extracellular Na+ (n = 4) but persist in recordings ma de with electrodes containing a blocker of voltage-gated Na+ channels (n = 7). These procedures cause similar effects on CCh-induced depolarizing plat eau potentials that are contributed by a Ca2+-activated nonselective cation ic conductance (I-CAN). Network and intrinsic oscillations along with depol arizing plateau potentials were abolished by the muscarinic receptor antago nist atropine. In conclusion, our findings demonstrate that low-frequency o scillations in the rat subiculum rely on the muscarinic receptor-dependent activation of an intrinsic oscillatory mechanism that is presumably contrib uted by I-CAN and are integrated within the network via non-NMDA receptor-m ediated transmission.