Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb.
Cholinergic axons and nicotinic receptors are abundant in all layers of the olfactory bulb (OB), the main region of newborn neuron integration in the adult brain. Here, we report that the OB granule cell layer in mice lacking the predominant form of brain high-affinity nicotinic acetylcholine receptors (beta(2)(-/-) mice) displayed nearly 50% more newborn neurons and significantly fewer apoptotic cells than did beta(2)(+/+) mice. Conversely, in vivo chronic nicotine exposure significantly decreased the number of newborn granule cells in beta(2)(+/+) but not beta(2)(-/-) adult mice, confirming that the survival of newborn neurons can be controlled by the activation of beta(2)-containing nicotinic acetylcholine receptors. Unexpectedly, investigating the behavioral consequence of an increased number of granule cells in beta(2)(-/-) mice revealed that these animals have a less robust short-term olfactory memory than their wild-type counterparts. Taken together, these results provide evidence that high-affinity nicotinic receptors are involved in the maturation of adult OB local circuits. They also indicate that an increase in the number of granule cells does not necessarily correlate with better olfactory performance and further highlight the importance of cholinergic afferents for olfactory processing.
Mechawar
Naguib
N
Receptors and Cognition Unit, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2182, Pasteur Institute, 75724 Paris Cedex 15, France.
Saghatelyan
Armen
A
Grailhe
Régis
R
Scoriels
Linda
L
Gheusi
Gilles
G
Gabellec
Marie-Madeleine
MM
Lledo
Pierre-Marie
PM
Changeux
Jean-Pierre
JP
D000375:Aging; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D017353:Gene Deletion; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology; D009830:Olfactory Bulb / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology
D009538:Nicotine; D011978:Receptors, Nicotinic