Impairment of select forms of spatial memory and neurotrophin-dependent synaptic plasticity by deletion of glial aquaporin-4
| Autor: | Barbara L. Hempstead, Devin K. Binder, Qi Cheng, Marcelo A. Wood, Helen E. Scharfman, Andrew Treister, Vanessa A. Skucas, Jianmin Yang, Aine M. Duffy, Ian B. Mathews, Alan S. Verkman |
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| Rok vydání: | 2011 |
| Předmět: |
Patch-Clamp Techniques
Biophysics Carbazoles Morris water navigation task Action Potentials Stimulation Tropomyosin receptor kinase B Biology In Vitro Techniques Article Indole Alkaloids Mice Animals Immunoprecipitation Receptor trkB Enzyme Inhibitors Maze Learning Long-Term Synaptic Depression Brain-derived neurotrophic factor Aquaporin 4 Mice Knockout Memory Disorders Chi-Square Distribution Neuronal Plasticity General Neuroscience musculoskeletal neural and ocular physiology Brain-Derived Neurotrophic Factor Long-term potentiation Electric Stimulation Disease Models Animal nervous system Trk receptor Synaptic plasticity sense organs Neuroscience Neuroglia Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 31(17) |
| ISSN: | 1529-2401 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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