title: Mutation of the HERC 1 Ubiquitin Ligase Impairs Associative Learning in the Lateral Amygdala.
abstract: Tambaleante (tbl/tbl) is a mutant mouse that carries a spontaneous Gly483Glu substitution in the HERC1 (HECT domain and RCC1 domain) E3 ubiquitin ligase protein (HERC1). The tbl/tbl mutant suffers an ataxic syndrome given the almost complete loss of cerebellar Purkinje cells during adult life. More recent analyses have identified alterations at neuromuscular junctions in these mice, as well as in other neurons of the central nervous system, such as motor neurons in the spinal cord, or pyramidal neurons in the hippocampal CA3 region and the neocortex. Accordingly, the effect of the tbl/tbl mutation apparently extends to other regions of the nervous system far from the cerebellum. As HERC1 mutations in humans have been correlated with intellectual impairment, we studied the effect of the tbl/tbl mutation on learning. Using a behavioral test, ex vivo electrophysiological recordings, immunohistochemistry, and Golgi method, we analyzed the associative learning in the lateral amygdala of the tbl/tbl mouse. The tbl/tbl mice perform worse than wild-type animals in the passive avoidance test, and histologically, the tbl/tbl mice have more immature forms of dendritic spines. In addition, LTP cannot be detected in these animals and their STP is dampened, as is their glutamatergic input to the lateral amygdala. Together, these data suggest that HERC1 is probably involved in regulating synaptic function in the amygdala. Indeed, these results indicate that the tbl/tbl mutation is a good model to analyze the effect of alterations to the ubiquitin-proteasome pathway on the synaptic mechanisms involved in learning and its defects.
authors.affiliation: Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, Ctra Utrera km. 1, 41013, Seville, Spain.
authors.forename: Eva Mª
authors.initials: EM
authors.lastname: Pérez-Villegas
authors.affiliation: Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, Ctra Utrera km. 1, 41013, Seville, Spain.|División de Ciencias de la Salud e Ingenierías, Universidad de Guanajuato, Campus Celaya-Salvatierra, Guanajuato, Mexico.
authors.forename: José V
authors.initials: JV
authors.lastname: Negrete-Díaz
authors.affiliation: Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, Ctra Utrera km. 1, 41013, Seville, Spain.
authors.forename: Mª Elena
authors.initials: ME
authors.lastname: Porras-García
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Seville, 41012, Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ruiz
authors.affiliation: Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, Ctra Utrera km. 1, 41013, Seville, Spain.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Carrión
authors.affiliation: Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, Ctra Utrera km. 1, 41013, Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Moreno
authors.affiliation: Department of Physiology, Anatomy and Cell Biology, University Pablo de Olavide, Ctra Utrera km. 1, 41013, Seville, Spain. jaarmbut@upo.es.
authors.forename: José A
authors.identifier: 0000-0002-9452-7828
authors.initials: JA
authors.lastname: Armengol
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C547877:HERC1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Amygdala; Dendritic spines; Glutamatergic input; HERC1; LTP; Learning; Synapses; tambaleante