title: Generation of dendritic Ca2+ oscillations as a consequence of altered ryanodine receptor function in AD neurons.
abstract: Ryanodine receptor (RyR)-mediated Ca(2+) dysregulation is associated with Alzheimer's disease (AD) neuropathology. Using 2-photon Ca(2+) imaging and patch clamp recordings in brain slice preparations from young 3xTg-AD and NonTg control mice, we recently demonstrated that RyR-mediated Ca(2+) -induced Ca(2+) release (CICR) is substantially increased within dendrites from AD neurons, such that synaptic stimulation alone is sufficient to generate aberrant CICR. We also observed supra-additive Ca(2+) release upon coincident RyR activation with synaptic stimulation in 3xTg-AD mice. Here, we describe an additional observed phenomenon: generation of patterned Ca(2+) oscillations in the spines and dendrites from AD neurons upon coincident RyR and synaptic stimulation. As the temporal entrainment of Ca(2+) signals influences many downstream cellular and synaptic functions, these abnormal oscillatory patterns may be associated with the structural and functional breakdown of synapses in AD.
authors.affiliation: Department of Pediatrics, Section of Neurology, University of Chicago, IL USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Goussakov
authors.forename: Shreaya
authors.initials: S
authors.lastname: Chakroborty
authors.forename: Grace E
authors.initials: GE
authors.lastname: Stutzmann
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission; D013997:Time Factors
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine