Nicotinic modulation of network and synaptic transmission in the immature hippocampus investigated with genetically modified mice.
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 alpha7 and beta2-containing (alpha7* and beta2*) 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), alpha7-/- and beta2-/- mice. We found that alpha7* and beta2* 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, alpha7* but not beta2* 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 alpha7* and beta2* nAChRs exert a fine regional modulation of GABAergic and glutamatergic transmission that underlies nicotine-elicited changes in network synchronization.
Le Magueresse
Corentin
C
Neurobiology Department, International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste, Italy.
Safiulina
Victoria
V
Changeux
Jean-Pierre
JP
Cherubini
Enrico
E
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005731:Ganglionic Stimulants; D005971:Glutamates; D011978:Receptors, Nicotinic; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D000109:Acetylcholine