Impairment of select forms of spatial memory and neurotrophin-dependent synaptic plasticity by deletion of glial aquaporin-4

Vanessa A. Skucas, Ian B. Mathews, Jianmin Yang, Qi Cheng, Andrew Treister, Aine M. Duffy, Alan S. Verkman, Barbara L. Hempstead, Marcelo A. Wood, Devin K. Binder, Helen E. Scharfman

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Aquaporin-4(AQP4)is the major water channel in the CNS and is primaril expressed in a strocytes. Little is known about the potential for AQP4toinfluence synaptic plasticity, although many studies have shown that it regulates the response of the CNS to injury. Therefore, we evaluated long-termpotentiation (LTP) and long-term depression (LTD)inAQP4knock-out (KO) and wild-type mice. KO mice exhibited a selective defect in LTP and LTD without a change in basal transmission or short-term plasticity. Interestingly, the impairment in LTP in KO mice was specific for the type of LTP that depends on the neurotroph in BDNF, which is induced by stimulation at theta rhythm [theta-burst stimulation (TBS)-LTP], but there was no impairment in a form of LTP that is BDNF independent, induced by high-frequency stimulation. LTD was also impaired in KO mice, which was rescued by ascavenger of BDNF or blockade of Trk receptors. TrkB receptors, which mediate effects of BDNF on TBS-LTP, were notaltered in KO mice, but p75NTR,the receptor that binds all neurotrophins and has been implicated in some types of LTD, was decreased. The KOmice also exhibitedacognitive defect, which suggests anew role for AQP4 andastrocytesinnormal cognitive function. This defect was evidentusingatest for location-specific object memory but not Morris water maze or contextual fear conditioning. The results suggest that AQP4 channels in astrocytes play an unanticipated role in neurotrophin-dependent plasticity and influence behavior.

Original languageEnglish (US)
Pages (from-to)6392-6397
Number of pages6
JournalJournal of Neuroscience
Issue number17
StatePublished - Apr 27 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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