Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity.
This study reveals mechanisms in the mouse hippocampus that may underlie nicotinic influences on attention, memory, and cognition. Induction of synaptic plasticity, arising via generally accepted mechanisms, is modulated by nicotinic acetylcholine receptors. Properly timed nicotinic activity at pyramidal neurons boosted the induction of long-term potentiation via presynaptic and postsynaptic pathways. On the other hand, nicotinic activity on interneurons inhibited nearby pyramidal neurons and thereby prevented or diminished the induction of synaptic potentiation. The synaptic modulation was dependent on the location and timing of the nicotinic activity. Loss of these synaptic mechanisms may contribute to the cognitive deficits experienced during Alzheimer's diseases, which is associated with a loss of cholinergic projections and with a decrease in the number of nicotinic receptors.
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Division of Neuroscience and, Structural and Computational Biology and Molecular Biophysics Program, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA. jdani@bcm.tmc.edu
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000503:physiopathology; D019943:Amino Acid Substitution; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008464:Mecamylamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D000109:Acetylcholine; D001640:Bicuculline