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Muscarinic control of dendritic excitability and Ca(2+) signaling in CA1 pyramidal neurons in rat hippocampal slice.

Abstract：

:The cholinergic system is critically involved in synaptic models of learning and memory by enhancing dendritic [Ca(2+)](i) signals. Diffuse cholinergic innervation suggests subcellular modulation of membrane currents and Ca(2+) signals. Here we use ion-selective microelectrodes to study spread of carbachol (CCh) after focal application into brain slice and subcellular muscarinic modulation of synaptic responses in CA1 pyramidal neurons. Proximal application of CCh rapidly blocked the somatic slow afterhyperpolarization (sAHP) following repetitive stimulation. In contrast, the time course of potentiation of the slow tetanic depolarization (STD) during synaptic input was slower and followed the time course of spread of CCh to the dendritic tree. With distal application, augmentation of the somatic STD and of dendritic Ca(2+) responses followed spread of CCh to the entire apical dendritic tree, whereas the sAHP was blocked only after spread of CCh to the proximal dendritic segment. In dendritic recordings, CCh blocked a small sAHP, augmented the STD, and rather reduced dendritic action potentials. Augmentation of dendritic Ca(2+) signals was highly correlated to augmentation of the STD. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) blocked approximately 55% of the STD in control and during CCh application. In conclusion, muscarinic suppression of the proximal sAHP can augment firing and thereby Ca(2+) responses. Dendritic augmentation of the STD by blockade of the sAHP and direct enhancement of N-methyl-D-aspartate (NMDA) receptor-mediated currents potentiates Ca(2+) signals even when firing is not affected due to suprathreshold input. In this way, subcellular muscarinic modulation may contribute to parallel information processing and storage by dendritic synapses of CA1 pyramidal neurons.

journal_name

J Neurophysiol

journal_title

Journal of neurophysiology

authors

Egorov AV,Gloveli T,Müller W

doi

10.1152/jn.1999.82.4.1909

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

1909-15

issue

eissn

0022-3077

issn

1522-1598

journal_volume

pub_type

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Muscarinic control of dendritic excitability and Ca(2+) signaling in CA1 pyramidal neurons in rat hippocampal slice.