Skip to Content
Merck

Increasing SK2 channel activity impairs associative learning.

Journal of neurophysiology (2012-05-04)
Bridget M McKay, M Matthew Oh, Roberto Galvez, Jeffrey Burgdorf, Roger A Kroes, Craig Weiss, John P Adelman, Joseph R Moskal, John 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 learning and further support postburst AHP reductions in hippocampal pyramidal neurons as a biomarker of successful learning.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-KCNN2 antibody produced in rabbit, IgG fraction of antiserum
Pricing and availability is not currently available.
Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Pricing and availability is not currently available.
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Pricing and availability is not currently available.
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 3, DMSO solution
Pricing and availability is not currently available.