Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Apr 27;31(17):6392-7.
doi: 10.1523/JNEUROSCI.6249-10.2011.

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

Vanessa A Skucas  1 , 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
Affiliations

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

Vanessa A Skucas et al. J Neurosci. .

Abstract

Aquaporin-4 (AQP4) is the major water channel in the CNS and is primarily expressed in astrocytes. Little is known about the potential for AQP4 to influence synaptic plasticity, although many studies have shown that it regulates the response of the CNS to injury. Therefore, we evaluated long-term potentiation (LTP) and long-term depression (LTD) in AQP4 knock-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 neurotrophin 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 a scavenger of BDNF or blockade of Trk receptors. TrkB receptors, which mediate effects of BDNF on TBS-LTP, were not altered in KO mice, but p75NTR, the receptor that binds all neurotrophins and has been implicated in some types of LTD, was decreased. The KO mice also exhibited a cognitive defect, which suggests a new role for AQP4 and astrocytes in normal cognitive function. This defect was evident using a test 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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Selective impairments in synaptic plasticity in AQP4 KO mice. A1, Superimposed fEPSPs evoked with increasing stimulus intensities (by increasing the duration of the stimulus, in microseconds) show similar responses in WT and KO mice. A2, Quantified fEPSP slopes show similarity of WT and KO mice. A3, Similarity of paired-pulse facilitation of fEPSP slope (half-maximal stimuli) in WT and KO mice. B, Top, Similar sPSCs in WT and KO pyramidal cells. Bottom, Cumulative frequency plots did not demonstrate differences in genotypes. C, Comparison of TBS-LTP in WT (black) and KO (white) mice. D, Comparison of LTD in WT and KO mice. E, Comparison of HFS-LTP in WT and KO mice. Arrows denote TBS and HFS; LFS is marked by the bar. Additional data are in the text; also, see Notes.
Figure 2.
Figure 2.
Selective OP deficit in KO mice. A, In the MWM, there were no significant differences in the average time to locate the hidden platform, plotted for each day animals were tested. Inset, There were no differences between genotypes in the probe trial (1, 2, 3, and 4 reflect each quadrant; 4 = target quadrant; see Notes). Note that CD1 mice normally do not exhibit a preference for the target quadrant in the probe trial (Adams et al., 2002). B, In CFC, there were no significant differences between WT and KO mice in the conditioning or testing trials. C, KO mice were impaired in OP because they did not spend more time in trial 2 exploring the moved object, but WT mice did.
Figure 3.
Figure 3.
Neurotrophin signaling in WT and KO mice. A1,TrkB-Fc rescued LTD in KO mice. Slices from KO mice were exposed (thick bar) to TrkB-Fc or control IgG for 15 min before and after LFS. A2, K252a rescued LTD in KO mice. Experiments analogous to those in A were conducted, except the slices were exposed to K252a (300 nm) or vehicle (0.05% DMSO). B1, Full-length (F) and truncated (T) TrkB levels were not significantly different in WT and KO mice. B2, WT mice had reduced p75NTR receptor levels.
See this image and copyright information in PMC

References

    1. Adams B, Fitch T, Chaney S, Gerlai R. Altered performance characteristics in cognitive tasks: comparison of the albino ICR and CD1 mouse strains. Behav Brain Res. 2002;133:351–361. - PubMed
    1. Aicardi G, Argilli E, Cappello S, Santi S, Riccio M, Thoenen H, Canossa M. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor. Proc Natl Acad Sci U S A. 2004;101:15788–15792. - PMC - PubMed
    1. Akaneya Y, Tsumoto T, Hatanaka H. Brain-derived neurotrophic factor blocks long-term depression in rat visual cortex. J Neurophysiol. 1996;76:4198–4201. - PubMed
    1. Angelo MF, Aviles-Reyes RX, Villarreal A, Barker P, Reines AG, Ramos AJ. P75 NTR expression is induced in isolated neurons of the penumbra after ischemia by cortical devascularization. J Neurosci Res. 2009;87:1892–1903. - PubMed
    1. Assini FL, Duzzioni M, Takahashi RN. Object location memory in mice: Pharmacological validation and further evidence of hippocampal CA1 participation. Behav Brain Res. 2009;204:206–211. - PubMed

Publication types

MeSH terms