title: Mechanisms generating dual-component nicotinic EPSCs in cortical interneurons.
abstract: Activation of cortical nicotinic receptors by cholinergic axons from the basal forebrain (BF) significantly impacts cortical function, and the loss of nicotinic receptors is a hallmark of aging and neurodegenerative disease. We have previously shown that stimulation of BF axons generates a fast α7 and a slow non-α7 receptor-dependent response in cortical interneurons. However, the synaptic mechanisms that underlie this dual-component nicotinic response remain unclear. Here, we report that fast α7 receptor-mediated EPSCs in the mouse cortex are highly variable and insensitive to perturbations of acetylcholinesterase (AChE), while slow non-α7 receptor-mediated EPSCs are reliable and highly sensitive to AChE activity. Based on these data, we propose that the fast and slow nicotinic responses reflect differences in synaptic structure between cholinergic varicosities activating α7 and non-α7 classes of nicotinic receptors.
authors.affiliation: Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Corbett
authors.initials: C
authors.lastname: Bennett
authors.forename: Sergio
authors.initials: S
authors.lastname: Arroyo
authors.forename: Dominic
authors.initials: D
authors.lastname: Berns
authors.forename: Shaul
authors.initials: S
authors.lastname: Hestrin
mesh_terms: D000110:Acetylcholinesterase / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D059329:Cholinergic Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D011978:Receptors, Nicotinic; D000110:Acetylcholinesterase