title: Acute cholinergic rescue of synaptic plasticity in the neurodegenerating cortex of anti-nerve-growth-factor mice.
abstract: Deficits in cholinergic systems innervating cerebral cortex are associated with cognitive impairment during senescence and in age-related neurodegenerative pathologies. However, little is known about the role of cholinergic pathways in modulating cortical plasticity. Basal forebrain cholinergic neurons are a major target for nerve-growth factor (NGF). In order to investigate the relationship between cholinergic innervation and cortical synaptic plasticity, we exploited a transgenic mouse model in which the activity of NGF in the adult nervous system is neutralized by the expression of blocking antibodies to NGF itself (anti-NGF mice) [Ruberti, F. et al. (2000). J. Neurosci. 20, 2589-2601]. In 6-month-old anti-NGF mice, we show that the reduction in cholinergic innervation of the cortex is associated with different forms of synaptic plasticity impairment. A local, acute increase in the availability of acetylcholine rescues these synaptic plasticity deficits, thus indicating that a cholinergic system mediates the impairment of cortical plasticity at this early stage of the neurodegenerative process triggered by NGF neutralization. Our results represent an important step in unveiling the pivotal role of cholinergic transmission in modulating adult cortical plasticity.
authors.affiliation: Neuroscience Program, SISSA (International School of Advanced Studies), Via Beirut 2-4, 34014 Trieste, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pesavento
authors.forename: Simona
authors.initials: S
authors.lastname: Capsoni
authors.forename: Luciano
authors.initials: L
authors.lastname: Domenici
authors.forename: Antonino
authors.initials: A
authors.lastname: Cattaneo
mesh_terms: D000109:Acetylcholine / Q000172:deficiency* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018679:Cholinergic Agonists / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004558:Electric Stimulation; D058787:GABA-A Receptor Antagonists; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000172:deficiency* / Q000276:immunology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018679:Cholinergic Agonists; D058787:GABA-A Receptor Antagonists; D008869:Microtubule-Associated Proteins; D011963:Receptors, GABA-A; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine