CPT1C is required for synaptic plasticity and oscillatory activity that supports motor, associative and non-associative learning
Autor/a
Iborra-Lázaro, Guillermo
Djebari, Souhail
Sánchez-Rodríguez, Irene
Gratacòs-Batlle, Esther
Sánchez-Fernández, Nuria
Radošević, Marija
Casals, Núria
Navarro-López, Juan de Dios
Soto del Cerro, David
Jiménez-Díaz, Lydia
Data de publicació
2023ISSN
0022-3751
Resum
Carnitine palmitoyltransferase 1c (CPT1C) is a neuron-specific protein widely distributed throughout the CNS and highly expressed in discrete brain areas including the hypothalamus, hippocampus, amygdala and different motor regions. Its deficiency has recently been shown to disrupt dendritic spine maturation and AMPA receptor synthesis and trafficking in the hippocampus, but its contribution to synaptic plasticity and cognitive learning and memory processes remains mostly unknown. Here, we aimed to explore the molecular, synaptic, neural network and behavioural role of CPT1C in cognition-related functions by using CPT1C knockout (KO) mice. CPT1C-deficient mice showed extensive learning and memory deficits. The CPT1C KO animals exhibited impaired motor and instrumental learning that seemed to be related, in part, to locomotor deficits and muscle weakness but not to mood alterations. In addition, CPT1C KO mice showed detrimental hippocampus-dependent spatial and habituation memory, most probably attributable to inefficient dendritic spine maturation, impairments in long-term plasticity at the CA3–CA1 synapse and aberrant cortical oscillatory activity. In conclusion, our results reveal that CPT1C is not only crucial for motor function, coordination and energy homeostasis, but also has a crucial role in the maintenance of learning and memory cognitive functions.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
Anglès
Matèries (CDU)
61 - Medicina
Paraules clau
CPT1C
Ex vivo
Prova d'habituació
Hipocamp
In vivo
Activitat locomotora
Potenciació a llarg termini
Ratolí
Nova ubicació d'objectes
Condicionament operant
Activitat oscil·latòria
CPT1C
Ex vivo
Prueba de habituación
Hipocampo
In vivo
Actividad locomotora
Potenciación a largo plazo
Ratón
Localización de objetos novedosos
Condicionamiento operante
Actividad oscilatoria
CPT1C
Ex vivo
Habituation test
Hippocampus
In vivo
Locomotor activity
Long-term potentiation
Mouse
Novel objectlocation
Operant conditioning
Oscillatory activity
Pàgines
24
Publicat per
Wiley
Col·lecció
16
Publicat a
The Journal of Physiology
Citació
Iborra-Lázaro, Guillermo; Djebari, Souhail; Sánchez-Rodríguez, Irene [et al.]. CPT1C is required for synaptic plasticity and oscillatory activity that supports motor, associative and non-associative learning. The Journal of Physiology, 2023, 16, p. 3533-3556. Disponible en: <https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP284248>. Fecha de acceso: 7 nov 2023. DOI: 10.1113/JP284248
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Drets
© 2023 The Authors.The Journal of Physiologypublished by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, whichpermits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and nomodifications or adaptations are made.
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