title: Activity-dependent localization in spines of the F-actin capping protein CapZ screened in a rat model of dementia.
abstract: Actin reorganization in dendritic spines is hypothesized to underlie neuronal plasticity. Actin-related proteins, therefore, might serve as useful markers of plastic changes in dendritic spines. Here, we utilized memory deficits induced by fimbria-fornix transection (FFT) in rats as a dementia model to screen candidate memory-associated molecules by using a two-dimensional gel method. Comparison of protein profiles between the transected and control sides of hippocampi after unilateral FFT revealed a reduction in the F-actin capping protein (CapZ) signal on the FFT side. Subsequent immunostaining of brain sections and cultured hippocampal neurons revealed that CapZ localized in dendritic spines and the signal intensity in each spine varied widely. The CapZ content decreased after suppression of neuronal firing by tetrodotoxin treatment in cultured neurons, indicating rapid and activity-dependent regulation of CapZ accumulation in spines. To test input specificity of CapZ accumulation in vivo, we delivered high-frequency stimuli to the medial perforant path unilaterally in awake rats. This path selectively inputs to the middle molecular layer of the dentate gyrus, where CapZ immunoreactivity increased. We conclude that activity-dependent, synapse-specific regulation of CapZ redistribution might be important in both maintenance and remodeling of synaptic connections in neurons receiving specific spatial and temporal patterns of inputs.
authors.affiliation: The University of Tokyo, Bunkyo-ku, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kitanishi
authors.forename: Jun
authors.initials: J
authors.lastname: Sakai
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukaya
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
authors.forename: Maki K
authors.initials: MK
authors.lastname: Yamada
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051347:CapZ Actin Capping Protein / Q000032:analysis / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D020712:Fornix, Brain / Q000166:cytology / Q000601:surgery; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism
chemical_list: D000199:Actins; D051347:CapZ Actin Capping Protein