Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo.
The dendritic spine is an important site of neuronal plasticity and contains extremely high levels of cytoskeletal actin. However, the dynamics of the actin cytoskeleton during synaptic plasticity and its in vivo function remain unclear. Here we used an in vivo dentate gyrus LTP model to show that LTP induction is associated with actin cytoskeletal reorganization characterized by a long-lasting increase in F-actin content within dendritic spines. This increase in F-actin content is dependent on NMDA receptor activation and involves the inactivation of actin depolymerizing factor/cofilin. Inhibition of actin polymerization with latrunculin A impaired late phase of LTP without affecting the initial amplitude and early maintenance of LTP. These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP.
Fukazawa
Yugo
Y
Mitsubishi Kagaku Institute of Life Sciences (MITILS), Machida, 194-8511, Tokyo, Japan.
Saitoh
Yoshito
Y
Ozawa
Fumiko
F
Ohta
Yasuhiko
Y
Mizuno
Kensaku
K
Inokuchi
Kaoru
K
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008959:Models, Neurological; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D051339:Actin Depolymerizing Factors; D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008840:Microfilament Proteins; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; C503969:Synpo protein, rat; D013844:Thiazoles; D053778:Thiazolidines; C053386:drebrins; C037067:latrunculin A