Chronically Increased G[subscript s][alpha] Signaling Disrupts Associative and Spatial Learning

Autor/inn/en	Bourtchouladze, Rusiko; Patterson, Susan L.; Kelly, Michele P.; Kreibich, Arati; Kandel, Eric R.; Abel, Ted
Titel	Chronically Increased G[subscript s][alpha] Signaling Disrupts Associative and Spatial Learning
Quelle	In: Learning & Memory, 13 (2006) 6, S.745-752 (8 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1072-0502
DOI	10.1101/lm.354106
Schlagwörter	Memory; Exhibits; Animals; Associative Learning; Spatial Ability; Learning Processes; Genetics; Physiology; Animal Behavior; Neurological Organization; Brain; Task Analysis; Conditioning; Cues + Suchen Sie Ihr Suchwort? Gedächtnis; Animal; Tier; Tiere; Räumliches Vorstellungsvermögen; Learning process; Lernprozess; Humangenetik; Physiologie; Tierverhalten; Gehirn; Aufgabenanalyse; Stichwort
Abstract	The cAMP/PKA pathway plays a critical role in learning and memory systems in animals ranging from mice to "Drosophila" to "Aplysia." Studies of olfactory learning in "Drosophila" suggest that altered expression of either positive or negative regulators of the cAMP/PKA signaling pathway beyond a certain optimum range may be deleterious. Here we provide genetic evidence of the behavioral and physiological effects of increased signaling through the cAMP/PKA pathway in mice. We have generated transgenic mice in which the expression of a constitutively active form of G[subscript s][alpha](G[subscript s][alpha]* Q227L), the G protein that stimulates adenylyl cyclase activity, is driven in neurons within the forebrain by the promoter from the CaMKII[alpha] gene. Despite significantly increased adenylyl cyclase activity, G[subscript s][alpha]* transgenic mice exhibit PKA-dependent decreases in levels of cAMP due to a compensatory up-regulation in phosphodiesterase activity. Interestingly, G[subscript s][alpha]* transgenic mice also exhibit enhanced basal synaptic transmission. Consistent with a role for the cAMP/PKA pathway in learning and memory, G[subscript s][alpha]* transgenic mice show impairments in spatial learning in the Morris water maze and in contextual and cued fear conditioning tasks. The learning deficits observed in these transgenic mice suggest that associative and spatial learning requires regulated G[subscript s][alpha] protein signaling, much as does olfactory learning in "Drosophila." (Author).
Anmerkungen	Cold Spring Harbor Laboratory Press. 500 Sunnyside Boulevard, Woodbury, NY 11797-2924. Tel: 800-843-4388; 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://www.learnmem.org/
Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10