title: Elimination of Kalrn expression in POMC cells reduces anxiety-like behavior and contextual fear learning.
abstract: Kalirin, a Rho GDP/GTP exchange factor for Rac1 and RhoG, is known to play an essential role in the formation and maintenance of excitatory synapses and in the secretion of neuropeptides. Mice unable to express any of the isoforms of Kalrn in cells that produce POMC at any time during development (POMC cells) exhibited reduced anxiety-like behavior and reduced acquisition of passive avoidance behavior, along with sex-specific alteration in the corticosterone response to restraint stress. Strikingly, lack of Kalrn expression in POMC cells closely mimicked the effects of global Kalrn knockout on anxiety-like behavior and passive avoidance conditioning without causing the other deficits noted in Kalrn knockout mice. Our data suggest that deficits in excitatory inputs onto POMC neurons are responsible for the behavioral phenotypes observed.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States.
authors.forename: Prashant
authors.initials: P
authors.lastname: Mandela
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States.
authors.forename: Taylor
authors.initials: T
authors.lastname: LaRese
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States.
authors.forename: Betty A
authors.initials: BA
authors.lastname: Eipper
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States. Electronic address: mains@uchc.edu.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Mains
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000523:psychology*; D001522:Behavior, Animal; D003345:Corticosterone / Q000097:blood; D005239:Fear / Q000523:psychology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D019417:Hindlimb Suspension; D007858:Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C548820:KALRN protein, mouse; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D001616:beta-Galactosidase; D003345:Corticosterone
keywords: ACTH; Corticosterone; Cre-recombinase; Passive-avoidance; Pituitary