title: Spatial exploration induces ARC, a plasticity-related immediate-early gene, only in calcium/calmodulin-dependent protein kinase II-positive principal excitatory and inhibitory neurons of the rat forebrain.
abstract: Active behavior, such as exploring a novel environment, induces the expression of the immediate-early gene Arc (activity-regulated cytoskeletal associated protein, or Arg 3.1) in many brain regions, including the hippocampus, neocortex, and striatum. Arc messenger ribonucleic acid and protein are localized in activated dendrites, and Arc protein is required for the maintenance of long-term potentiation and memory consolidation. Although previous evidence suggests that Arc is expressed in neurons, there is no direct demonstration that only neurons can express Arc. Furthermore, there is no characterization of the main neuronal types that express Arc. The data reported here show that behavior- or seizure-induced Arc expression in the hippocampus, primary somatosensory cortex, and dorsal striatum of rats colocalizes only with neuronal (NeuN-positive) and not with glial (GFAP-positive) cells. Furthermore, Arc was found exclusively in non-GABAergic alpha-CaMKII-positive hippocampal and neocortical neurons of rats that had explored a novel environment. Some GAD65/67-positive neurons in these regions were observed to express Arc, but only after a very strong stimulus (electroconvulsive seizure). In the dorsal striatum, spatial exploration induced Arc only in GABAergic and alpha-CaMKII-positive neurons. Combined, these results show that although a very strong stimulus (seizure) can induce Arc in a variety of neurons, behavior induces Arc in the CaMKII-positive principal neurons of the hippocampus, neocortex, and dorsal striatum. These results, coupled with recent in vitro findings of interactions between Arc and CaMKII, are consistent with the hypothesis that Arc and CaMKII act as plasticity partners to promote functional and/or structural synaptic modifications that accompany learning.
authors.affiliation: Synapses and Cognitive Neuroscience Center and Department of Neurology, School of Medicine, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Almira
authors.initials: A
authors.lastname: Vazdarjanova
authors.forename: Victor
authors.initials: V
authors.lastname: Ramirez-Amaya
authors.forename: Nathan
authors.initials: N
authors.lastname: Insel
authors.forename: Thane K
authors.initials: TK
authors.lastname: Plummer
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Shoaib
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Dalia
authors.initials: D
authors.lastname: Mikhael
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.forename: John F
authors.initials: JF
authors.lastname: Guzowski
authors.forename: Carol A
authors.initials: CA
authors.lastname: Barnes
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology; D005106:Exploratory Behavior / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013003:Somatosensory Cortex / Q000166:cytology / Q000378:metabolism; D013028:Space Perception / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; C092069:activity regulated cytoskeletal-associated protein; D005680:gamma-Aminobutyric Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases