Nicotinic acetylcholine receptors (nAChRs) of the hippocampus have been thought to contribute to cognitive enhancement by cigarette smoking. Although positive modulation on cognitive functions is linked to the smoked, low-dose nicotine, the cellular correlate behind this modulation is unknown. It has been accepted that cellular mechanisms underlying plastic effects on memory involve the association of backpropagating action potentials (bAPs) with synaptic activity in the hippocampus. Here, we show the effects of low-dose (1 microM) nicotine on bAP-evoked Ca2+ transients in basal dendrites and spines of pyramidal neurons in rat hippocampal slices. Although nicotine application failed to have any direct effect in low concentration, it could significantly enhance bAP-evoked Ca2+ transients through presynaptic nAChRs located on axon terminals innervating pyramidal cells. The activation of these receptors is known to release neurotransmitters and induce postsynaptic currents. High-dose (250-500 microM) nicotine could induce firing and Ca2+ accumulation in spines. Large amplitude currents were observed occasionally (8 out of 18 cells) in voltage clamp recordings in response to pressure application of high-dose nicotine. This may explain the relatively low incidence of nicotine-induced firing (7 out of 27 cells) under current clamp. These data indicate that (i) activation of presynaptic nAChRs can modulate backreporting in dendrites of pyramidal neurons and (ii) there is a group of pyramidal neurons with higher nicotine-sensitivity, producing firing at strong stimulations. Our data revealed a subcellular effect of nicotine through regulation of Ca2+ levels in the computational units of pyramidal neurons.
(c) 2008 Wiley-Liss, Inc.