title: The X-linked inhibitor of apoptosis regulates long-term depression and learning rate.
abstract: Hippocampal long-term depression (LTD) is an active form of synaptic plasticity that is necessary for consolidation of spatial memory, contextual fear memory, and novelty acquisition. Recent studies have shown that caspases (CASPs) play an important role in NMDA receptor-dependent LTD and are involved in postsynaptic remodeling and synaptic maturation. In the present study, we examined the role of X-linked inhibitor of apoptosis (XIAP), a putative endogenous CASP inhibitor, in synaptic plasticity in the hippocampus. Analysis in acute brain slices and in cultured hippocampal neurons revealed that XIAP deletion increases CASP-3 activity, enhances α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization, sharply increases LTD, and significantly reduces synapse density. In vivo behaviors related to memory were also altered in XIAP(-/-) mice, with faster acquisition of spatial object location and increased fear memory observed. Together, these results indicate that XIAP plays an important physiologic role in regulating sublethal CASP-3 activity within central neurons and thereby facilitates synaptic plasticity and memory acquisition.-Gibon, J., Unsain, N., Gamache, K., Thomas, R. A., De Leon, A., Johnstone, A., Nader, K., Séguéla, P., Barker, P. A. The X-linked inhibitor of apoptosis regulates long-term depression and learning rate.
authors.affiliation: Biology Unit, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada;
authors.forename: Julien
authors.initials: J
authors.lastname: Gibon
authors.affiliation: Laboratorio de Neurobiología, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Unsain
authors.affiliation: Department of Psychology, McGill University, Montreal, Quebec, Canada; and.
authors.forename: Karine
authors.initials: K
authors.lastname: Gamache
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada;
authors.forename: Rhalena A
authors.initials: RA
authors.lastname: Thomas
authors.affiliation: Biology Unit, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada;
authors.forename: Andres
authors.initials: A
authors.lastname: De Leon
authors.affiliation: Biology Unit, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada;
authors.forename: Aaron
authors.initials: A
authors.lastname: Johnstone
authors.affiliation: Department of Psychology, McGill University, Montreal, Quebec, Canada; and.
authors.forename: Karim
authors.initials: K
authors.lastname: Nader
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; philippe.seguela@mcgill.ca.
authors.forename: Philippe
authors.initials: P
authors.lastname: Séguéla
authors.affiliation: Biology Unit, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; philip.barker@ubc.ca.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barker
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology
chemical_list: C107521:Birc4 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: AMPAR; XIAP; caspase-3; hippocampus; synaptic activity