Subcellular muscarinic enhancement of excitability and Ca2+-signals in CA1-dendrites in rat hippocampal slice

The cholinergic system is involved in Ca2+-dependent models of learning. To study subcellular modulation, we evoked 50-100 mu m long dendritic Ca2+-responses by focal pressure application of glutamate. These Ca2+-responses were augmented by +70% by focally applied carbachol. This atropine-sensitive augmentation started within 1 s concurrent to an augmentation of the glutamate-evoked somatic depolarization and firing. Tetrodotoxin reduced the Ca2+-response to glutamate by 60-80% while, after having restored the Ca2+-signal by increasing the application of glutamate, its muscarinic augmentation was reduced from +73 to +30%. Lithium (2 mM, >2 h) slowed and reduced augmentation of Ca2+-signals and blocked augmentation of the glutamate-evoked depolarization and firing, but not suppression of the slow after-hyperpolarization following repetitive discharge. Thus, several mechanisms contribute to muscarinic augmentation of Ca2+-signals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.