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Learn Mem. 2015 Jun 15;22(7):323-35. doi: 10.1101/lm.037820.114. Print 2015 Jul.

The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice.

Author information

1
Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, 72076 Tübingen, Germany.
2
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
3
Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, 72076 Tübingen, Germany robert.lukowski@uni-tuebingen.de peter.ruth@uni-tuebingen.de.

Abstract

Kcnt1 encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual development. In particular, recent findings have shown that human Slack mutations produce very severe intellectual disability and that Slack channels interact directly with the Fragile X mental retardation protein (FMRP), a protein that when missing or mutated results in Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism in humans. We have now analyzed a recently developed Kcnt1 null mouse model in several behavioral tasks to assess which aspects of memory and learning are dependent on Slack. We demonstrate that Slack deficiency results in mildly altered general locomotor activity, but normal working memory, reference memory, as well as cerebellar control of motor functions. In contrast, we find that Slack channels are required for cognitive flexibility, including reversal learning processes and the ability to adapt quickly to unfamiliar situations and environments. Our data reveal that hippocampal-dependent spatial learning capabilities require the proper function of Slack channels.

PMID:
26077685
PMCID:
PMC4478330
DOI:
10.1101/lm.037820.114
[Indexed for MEDLINE]
Free PMC Article

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