AhR Deletion Promotes Aberrant Morphogenesis and Synaptic Activity of Adult-Generated Granule Neurons and Impairs Hippocampus-Dependent Memory

Newborn granule cells are continuously produced in the subgranular zone of dentate gyrus throughout life. Once these cells mature, they integrate into pre-existing circuits modulating hippocampus-dependent memory. Subsequently, mechanisms controlling generation and maturation of newborn cells are es...

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Detalles Bibliográficos
Autores: Parra Gonzalo, Juan De La, Cuartero Desviat, María Isabel, Pérez Ruiz, Alberto, García Culebras, Alicia, Martín Herranz, Ricardo, Sánchez-Prieto Borja, José, García Segura, Juan Manuel, Lizasoaín Hernández, Ignacio, Moro Sánchez, María Ángeles
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/94497
Acceso en línea:https://hdl.handle.net/20.500.14352/94497
Access Level:acceso abierto
Palabra clave:612.82
Aryl hydrocarbon receptor
Dendrite arborization
Hippocampal memory
Newborn granule cells
Neurociencias (Biológicas)
2410 Biología Humana
Descripción
Sumario:Newborn granule cells are continuously produced in the subgranular zone of dentate gyrus throughout life. Once these cells mature, they integrate into pre-existing circuits modulating hippocampus-dependent memory. Subsequently, mechanisms controlling generation and maturation of newborn cells are essential for proper hippocampal function. Therefore, we have studied the role of aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, in hippocampus-dependent memory and granule neuronal morphology and function using genetic loss-of-function approaches based on constitutive and inducible-nestin AhR–/– mice. The results presented here show that the impaired hippocampus-dependent memory in AhR absence is not due to its effects on neurogenesis but to aberrant dendritic arborization and an increased spine density, albeit with a lower number of mature mushrooms spines in newborn granule cells, a finding that is associated with an immature electrophysiological phenotype. Together, our data strongly suggest that AhR plays a pivotal role in the regulation of hippocampal function, by controlling hippocampal granule neuron morphology and synaptic maturation.