RT Journal Article
T1 HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory
T2 La ubiquitina ligasa HERC1 es necesaria para el aprendizaje y la memoria en el hipocampo
A1 Pérez-Villegas, E.
A1 Pérez Rodríguez, Mikel
A1 Negrete Diaz, Jose Vicente
A1 Ruiz, Rocío
A1 Rosa, Jose Luis
A1 Álvarez de Toledo, Guillermo
A1 Rodríguez-Moreno, Antonio
A1 Armengol Butrón de Mújica, José Ángel
K1 Autophagy
K1 Dendritic spines
K1 Glutamatergic input
K1 Hippocampus
K1 LTP
K1 Synapses
AB Mutations in the human HERC1 E3 ubiquitin ligase protein develop intellectual disability. The tambaleante (tbl) mouse carries a HERC1 mutation characterized by cerebellar ataxia due of adult cerebellar Purkinje cells death by extensive autophagy. Our previous studies demonstrated that both the neuromuscular junction and the peripheral nerve myelin sheaths are also affected in this mutant. Moreover, there are signs of dysregulated autophagy in the central nervous system in the tbl mouse, affecting spinal cord motor neurons, and pyramidal neurons of the neocortex and the hippocampal CA3 region. The tbl mutation affects associative learning, with absence of short- and long-term potentiation in the lateral amygdala, altered spinogenesis in their neurons, and a dramatic decrease in their glutamatergic input. To assess whether other brain areas engaged in learning processes might be affected by the tbl mutation, we have studied the tbl hippocampus using behavioral tests, ex vivo electrophysiological recordings, immunohistochemistry, the Golgi-Cox method and transmission electron microscopy. The tbl mice performed poorly in the novel-object recognition, T-maze and Morris water mazetests. In addition, there was a decrease in glutamatergic input while the GABAergic one remains unaltered in the hippocampal CA1 region of tbl mice, accompanied by changes in the dendritic spines, and signs of cellular damage. Moreover, the proportions of immature and mature neurons in the dentate gyrus of the tbl hippocampus differ relative to the control mice. Together, these observations demonstrate the important role of HERC1 in regulating synaptic activity during learning.
PB Frontiers Media S.A.
YR 2020
FD 2020-11-19
LK https://hdl.handle.net/10433/25720
UL https://hdl.handle.net/10433/25720
LA en
NO Front. Neuroanat. 14:592797.
NO Departamento fisiología, anatomía y biología celular
DS RIO
RD May 9, 2026