RT Journal Article
T1 Mutation of the HERC 1 Ubiquitin Ligase Impairs Associative Learning in the Lateral Amygdala
A1 Pérez-Villegas, E.
A1 Negrete Diaz, Jose Vicente
A1 Porras García, María Elena
A1 Ruiz, Rocío
A1 Carrión Rodríguez, Ángel Manuel
A1 Rodríguez-Moreno, Antonio
A1 Armengol Butrón de Mújica, José Ángel
K1 Amygdala
K1 Glutamatergic input
K1 HERC1
K1 Learning
K1 LTP
K1 tambaleante
K1 Dendritic spines
K1 Synapses
AB 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.
PB Springer
YR 2018
FD 2018
LK https://hdl.handle.net/10433/22438
UL https://hdl.handle.net/10433/22438
LA en
NO Pérez-Villegas, E.M., Negrete-Díaz, J.V., Porras-García, M.E. et al. Mutation of the HERC 1 Ubiquitin Ligase Impairs Associative Learning in the Lateral Amygdala. Mol Neurobiol 55, 1157–1168 (2018). https://doi.org/10.1007/s12035-016-0371-8
NO Departamento de Fisiología, Anatomía y Biología Celular. Universidad Pablo de Olavide.
DS RIO
RD Apr 23, 2026