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NEUROSCIENCE |
1 Unité Récepteurs et Cognition, CNRS URA 2182, Institut Pasteur, 25–28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
2 Neurobiology Department, International School for Advanced Studies, Via Beirut 2–4, 34014 Trieste, Italy
The hippocampus, a key structure in learning and memory processes, receives a powerful cholinergic innervation from the septum and contains nicotinic acetylcholine receptors (nAChRs). Early in postnatal development, activation of nAChRs by nicotine or endogenous acetylcholine contributes to enhance synaptic signalling. Here, the patch-clamp technique was used to assess the contribution of 
7 and ß2-containing (7* and ß2*) nAChRs to nicotine-elicited modulation of GABAergic and glutamatergic activity at the network and single-cell level in the immature hippocampus of wild-type (WT), 7–/– and ß2–/– mice. We found that 7* and ß2* nAChRs were sufficient to modulate nicotine-induced increase in frequency of spontaneously occurring giant depolarizing potentials (GDPs), which are generated at the network level by the synergistic action of glutamate and depolarizing GABA, and thought to play a crucial role in neuronal wiring. However, 7* but not ß2* receptors were essential in nicotine-induced increase of interictal discharge frequency recorded after postnatal day 3 in the presence of bicuculline, when GABA shifted from the depolarizing to the hyperpolarizing direction. To correlate these observations with nicotine-elicited changes in synaptic transmission, we recorded spontaneous GABAergic and glutamatergic postsynaptic currents in pyramidal cells and interneurons localized in stratum oriens, stratum pyramidale and stratum radiatum, in slices obtained from WT and knock-out animals. We found that early in postnatal life 7* and ß2* nAChRs exert a fine regional modulation of GABAergic and glutamatergic transmission that underlies nicotine-elicited changes in network synchronization.
(Received 21 July 2006;
accepted after revision 7 August 2006;
first published online 10 August 2006)
Corresponding author E. Cherubini: Neurobiology Department, International School for Advanced Studies, Via Beirut 2–4, 34014 Trieste, Italy. Email: cher{at}sissa.it
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  J. Zhang and D. K. Berg Reversible inhibition of GABAA receptors by {alpha}7-containing nicotinic receptors on the vertebrate postsynaptic neurons J. Physiol., March 15, 2007; 579(3): 753 - 763. [Abstract] [Full Text] [PDF]
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 Z. Liu, R. A. Neff, and D. K. Berg Sequential Interplay of Nicotinic and GABAergic Signaling Guides Neuronal Development Science, December 8, 2006; 314(5805): 1610 - 1613. [Abstract] [Full Text] [PDF]
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