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1 Neuroscience Programme, International School for Advanced Studies, Via Beirut 24, 34014 Trieste, Italy
2 Unité de Neurobiologie Moléculaire, CNRS URA 2182, Institut Pasteur, 2528 Rue du Docteur Roux, 75724 Paris Cedex 15, France
Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed within the brain where they contribute to the regulation of higher cognitive functions. The loss of the cholinergic function in Alzheimer's disease patients, along with the well-known memory enhancing effect of nicotine, emphasizes the role of cholinergic signalling in memory functions. The hippocampus, a key structure in learning and memory, is endowed with nAChRs localized at pre- and postsynaptic levels. In previous work on the immature hippocampus we have shown that, at low probability (P) synapses, activation of
7 nAChRs by nicotine or by endogenously released acetylcholine persistently enhanced glutamate release and converted presynaptically silent synapses into functional ones. Here we show that in the same preparation, at high P synapses, nicotine induces long-term depression of AMPA- and NMDA-mediated synaptic currents. This effect was mediated by presynaptic
7- and ß2-containing receptors and was associated with an increase in the paired pulse ratio and in the coefficient of variation. High P synapses could be converted into low P and vice versa by changing the extracellular Ca2+/Mg2+ ratio. In these conditions nicotine was able to persistently potentiate or depress synaptic responses depending on the initial P-values. A bi-directional control of synaptic plasticity by nicotine would considerably enhance the computational properties of the network during a critical period of postnatal development thus contributing to sculpt the neuronal circuit.
(Received 22 April 2004;
accepted after revision 21 July 2004;
first published online 22 July 2004)
Corresponding author E. Cherubini: Neuroscience Programme, International School for Advanced Studies, Via Beirut 24, 34014 Trieste, Italy. Email: cher{at}sissa.it
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