HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory
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 neuro...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Neuroanatomy |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnana.2020.592797/full |
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| author | Eva M. Pérez-Villegas Mikel Pérez-Rodríguez José V. Negrete-Díaz José V. Negrete-Díaz Rocío Ruiz Rocío Ruiz Jose Luis Rosa Guillermo Alvarez de Toledo Antonio Rodríguez-Moreno José A. Armengol |
| author_facet | Eva M. Pérez-Villegas Mikel Pérez-Rodríguez José V. Negrete-Díaz José V. Negrete-Díaz Rocío Ruiz Rocío Ruiz Jose Luis Rosa Guillermo Alvarez de Toledo Antonio Rodríguez-Moreno José A. Armengol |
| author_sort | Eva M. Pérez-Villegas |
| collection | DOAJ |
| description | 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 maze tests. 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. |
| first_indexed | 2024-12-21T00:36:34Z |
| format | Article |
| id | doaj.art-4bb93eb56fe449ab9b12dfc78d031d91 |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-12-21T00:36:34Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-4bb93eb56fe449ab9b12dfc78d031d912022-12-21T19:21:47ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292020-11-011410.3389/fnana.2020.592797592797HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and MemoryEva M. Pérez-Villegas0Mikel Pérez-Rodríguez1José V. Negrete-Díaz2José V. Negrete-Díaz3Rocío Ruiz4Rocío Ruiz5Jose Luis Rosa6Guillermo Alvarez de Toledo7Antonio Rodríguez-Moreno8José A. Armengol9Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Seville, SpainDepartment of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Seville, SpainDepartment of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Seville, SpainDivisión de Ciencias de la Salud e Ingenierías, Universidad de Guanajuato, Guanajuato, MexicoDepartment of Biochemistry and Molecular Biology, School of Pharmacy, University of Seville, Seville, SpainInstituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, SpainDepartament de Ciències Fisiològiques, IBIDELL, Universitat de Barcelona, Barcelona, SpainDepartment of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville, SpainDepartment of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Seville, SpainDepartment of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Seville, SpainMutations 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 maze tests. 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.https://www.frontiersin.org/articles/10.3389/fnana.2020.592797/fullautophagydendritic spinesglutamatergic inputhippocampusLTPsynapses |
| spellingShingle | Eva M. Pérez-Villegas Mikel Pérez-Rodríguez José V. Negrete-Díaz José V. Negrete-Díaz Rocío Ruiz Rocío Ruiz Jose Luis Rosa Guillermo Alvarez de Toledo Antonio Rodríguez-Moreno José A. Armengol HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory Frontiers in Neuroanatomy autophagy dendritic spines glutamatergic input hippocampus LTP synapses |
| title | HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory |
| title_full | HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory |
| title_fullStr | HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory |
| title_full_unstemmed | HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory |
| title_short | HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory |
| title_sort | herc1 ubiquitin ligase is required for hippocampal learning and memory |
| topic | autophagy dendritic spines glutamatergic input hippocampus LTP synapses |
| url | https://www.frontiersin.org/articles/10.3389/fnana.2020.592797/full |
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