Increasing SK2 channel activity impairs associative learning.

Journal of Neurophysiology
Bridget M McKayJ F Disterhoft

Abstract

Enhanced intrinsic neuronal excitability of hippocampal pyramidal neurons via reductions in the postburst afterhyperpolarization (AHP) has been hypothesized to be a biomarker of successful learning. This is supported by considerable evidence that pharmacologic enhancement of neuronal excitability facilitates learning. However, it has yet to be demonstrated that pharmacologic reduction of neuronal excitability restricted to the hippocampus can retard acquisition of a hippocampus-dependent task. Thus, the present study was designed to address this latter point using a small conductance potassium (SK) channel activator NS309 focally applied to the dorsal hippocampus. SK channels are important contributors to intrinsic excitability, as measured by the medium postburst AHP. NS309 increased the medium AHP and reduced excitatory postsynaptic potential width of CA1 neurons in vitro. In vivo, NS309 reduced the spontaneous firing rate of CA1 pyramidal neurons and impaired trace eyeblink conditioning in rats. Conversely, trace eyeblink conditioning reduced levels of SK2 channel mRNA and protein in the hippocampus. Therefore, the present findings indicate that modulation of SK channels is an important cellular mechanism for associative lea...Continue Reading

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Citations

Mar 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lei ZhangSteven A Thomas
Mar 29, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bridget M McKayJohn F Disterhoft
Jul 26, 2013·Expert Opinion on Therapeutic Targets·Jenny LamHeike Wulff
May 4, 2013·Neuroscience and Biobehavioral Reviews·Kathryn D BakerNikki S Rickard
Feb 24, 2015·Brain Research·William C Buchta, Arthur C Riegel
Jul 23, 2013·Neurobiology of Learning and Memory·Megha SehgalJames R Moyer
Apr 23, 2013·Trends in Neurosciences·Sarah R HulmeWickliffe C Abraham
Apr 10, 2014·Frontiers in Behavioral Neuroscience·Marangelie Criado-MarreroJames T Porter
May 27, 2014·Frontiers in Systems Neuroscience·Nicolette OgnjanovskiSara J Aton
Aug 2, 2016·Behavioural Brain Research·Xiao-Wen YuJohn F Disterhoft
Nov 1, 2016·Journal of Neuroscience Research·Xin-Yi ChenYi-Feng Du
Jan 29, 2019·Frontiers in Molecular Neuroscience·Xin-Yi ChenLei Chen
Jul 25, 2019·Annual Review of Pharmacology and Toxicology·Brandon M BrownHeike Wulff
Jun 21, 2014·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·M Matthew Oh, John F Disterhoft
Aug 24, 2019·Neurobiology of Learning and Memory·Amy R Dunn, Catherine C Kaczorowski
Feb 26, 2021·Neurobiology of Learning and Memory·Arij Daou, Daniel Margoliash
Jul 7, 2017·Neuron·Heather K TitleyChristian Hansel

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