Muscarinic control of dendritic excitability and Ca2+ signaling in CA1 pyramidal neurons in rat hippocampal slice

The cholinergic system is critically involved in synaptic models of learnin g and memory by enhancing dendritic [Ca2+](i) signals. Diffuse cholinergic innervation suggests subcellular modulation of membrane currents and Ca2+ s ignals. Here we use ion-selective microelectrodes to study spread of carbac hol (CCh) after focal application into brain slice and subcellular muscarin ic modulation of synaptic responses in CAI pyramidal neurons. Proximal appl ication of CCh rapidly blocked the somatic slow afterhyperpolarization (sAH P) following repetitive stimulation. In contrast, the time course of potent iation of the slow tetanic depolarization (STD) during synaptic input was s lower and followed the time course of spread of CCh to the dendritic tree. With distal application, augmentation of the somatic STD and of dendritic C a2+ responses followed spread of CCh to the entire apical dendritic tree, w hereas the sAHP was blocked only after spread of CCh to the proximal dendri tic segment. In dendritic recordings, CCh blocked a small sAHP, augmented t he STD, and rather reduced dendritic action potentials. Augmentation of den dritic Ca2+ signals was highly correlated to augmentation of the STD. The N MDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) blocked si milar to 55% of the STD in control and during CCh application. In conclusio n, muscarinic suppression of the proximal sAHP can augment firing and there by Ca2+ responses. Dendritic augmentation of the STD by blockade of the sAH P and direct enhancement of N-methyl-D-aspartate (NMDA) receptor-mediated c urrents potentiates Ca2+ signals even when firing is not affected due to su prathreshold input. In this way, subcellular muscarinic modulation may cont ribute to parallel information processing and storage by dendritic synapses of CA1 pyramidal neurons.