title: Long-term potentiation in the rat dentate gyrus is associated with enhanced Arc/Arg3.1 protein expression in spines, dendrites and glia.
abstract: Electron microscopic immunocytochemical methods were used to determine the localization, subcellular distribution and expression of activity-regulated cytoskeletal protein (Arc/Arg3.1) in dentate gyrus after unilateral induction of long-term potentiation (LTP) in the perforant pathway of anaesthetized rats. At 2 h post-induction, immunoreaction product was visible in the dentate gyrus in both the granule cell and molecular layers. Arc expression was higher in the potentiated than the unstimulated contralateral hemisphere. Single-section electron microscopy analysis in unstimulated tissue and in tissue prepared 2 and 4 h after LTP induction showed Arc immunoreactivity (Arc-IR) in dendrites, dendritic spines and glia. Arc-IR was associated with synaptic and non-synaptic plasma membrane apposed to axon terminals and with cytoplasmic organelles, including the cytoskeleton. Arc-IR was also present in neuronal perikarya and there was occasional labelling of nuclei and axons. At 2 h post-LTP induction, there were significant increases in Arc-IR within the granule cell and molecular layers of the dentate gyrus and particularly within the middle molecular layer relative to the inner and outer molecular layers. This increase in Arc expression 2 h after LTP induction was blocked by the N-methyl-D-aspartate receptor antagonist (RS)-3-2-carboxypiperazin-4-yl-propyl-1-phosphonic acid. In animals killed 4 h after LTP induction, Arc expression had declined and differences between the potentiated and unpotentiated hemispheres were no longer significant. Our data provide ultrastructural evidence for a transient LTP-associated increase in the expression of Arc protein in the middle molecular layer of the dentate gyrus, with preferential targeting to dendrites, dendritic spines and glia.
authors.affiliation: Department of Biological Sciences, Faculty of Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK. j.j.rodrigues-arellano@open.ac.uk
authors.forename: J J
authors.initials: JJ
authors.lastname: Rodríguez
authors.forename: H A
authors.initials: HA
authors.lastname: Davies
authors.forename: A T
authors.initials: AT
authors.lastname: Silva
authors.forename: I E J
authors.initials: IE
authors.lastname: De Souza
authors.forename: C J
authors.initials: CJ
authors.lastname: Peddie
authors.forename: F M
authors.initials: FM
authors.lastname: Colyer
authors.forename: C L
authors.initials: CL
authors.lastname: Lancashire
authors.forename: A
authors.initials: A
authors.lastname: Fine
authors.forename: M L
authors.initials: ML
authors.lastname: Errington
authors.forename: T V P
authors.initials: TV
authors.lastname: Bliss
authors.forename: M G
authors.initials: MG
authors.lastname: Stewart
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C092069:activity regulated cytoskeletal-associated protein; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid