Significant structural but not physiological changes in cortical neurons of 12-month-old Tg2576 mice.
Amyloid-beta (Abeta) plays a key role in the etiology of Alzheimer's disease, and pyramidal cell dendrites exposed to Abeta exhibit dramatic structural alterations, including reduced dendritic spine densities. To determine whether such structural alterations lead to electrophysiological changes, whole-cell patch clamp recordings with biocytin filling were used to assess both the electrophysiological and morphological properties of layer 3 pyramidal cells in frontal cortical slices prepared from 12-month-old Tg2576 amyloid precursor protein (APP) mutant vs. wild-type (Wt) mice. Tg2576 cells exhibited significantly increased dendritic lengths and volumes and decreased spine densities, while the total number of spines was not different from Wt. Tg2576 and Wt cells did not differ with regard to passive membrane, action potential firing or glutamatergic spontaneous excitatory postsynaptic current properties. Thus, overexpression of mutated APP in young Tg2576 mice leads to significant changes in neuronal morphological properties which do not have readily apparent functional consequences.
Rocher
Anne B
AB
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA.
Kinson
Michael S
MS
Luebke
Jennifer I
JI
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D048429:Cell Size; D002540:Cerebral Cortex / Q000473:pathology*; D003712:Dendrites / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000473:pathology* / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D019809:Streptavidin / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D019809:Streptavidin