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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / deficiency*
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Acetylcholine / pharmacology
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / metabolism
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Animals
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Basal Nucleus of Meynert / metabolism*
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Basal Nucleus of Meynert / pathology
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Basal Nucleus of Meynert / physiopathology
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Cell Survival / drug effects
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Cell Survival / physiology
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Cerebral Cortex / metabolism*
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Cerebral Cortex / pathology
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Cerebral Cortex / physiopathology
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Choline O-Acetyltransferase / metabolism
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Cholinergic Agonists / pharmacology
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Cholinergic Fibers / drug effects
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Cholinergic Fibers / metabolism*
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Cholinergic Fibers / pathology
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Electric Stimulation
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GABA-A Receptor Antagonists
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Mice
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Mice, Transgenic
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Microtubule-Associated Proteins / metabolism
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism*
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Nerve Degeneration / physiopathology
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Nerve Growth Factor / deficiency*
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Nerve Growth Factor / immunology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / pathology
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Rats
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Receptors, GABA-A / metabolism
Substances
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Amyloid beta-Peptides
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Cholinergic Agonists
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GABA-A Receptor Antagonists
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Microtubule-Associated Proteins
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Receptors, GABA-A
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Nerve Growth Factor
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Choline O-Acetyltransferase
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Acetylcholine