Título : | Role of Adult-Born Neurons in Hippocampal Representations of Space |
Autor(es) : | Frechou Schandy, Maria Agustina |
Fecha de publicación : | 29-sep-2023 |
Tipo de publicación: | Tesis de doctorado |
Versión: | Publicado |
Supervisor(es) : | Goncalves, J. Tiago |
Publicado por: | Albert Einstein College of Medicine |
Areas del conocimiento : | Ciencias Médicas y de la Salud Medicina Básica Neurociencias |
Otros descriptores : | Neurogenesis Giro dentado Microscopia de 2 fotones Memoria espacial |
Resumen : | Adult neurogenesis is a unique form of neuronal plasticity in which newly generated neurons are integrated into the adult dentate gyrus in a process modulated by environmental stimuli. Adult-born neurons can contribute to spatial memory, but it is unknown how they contribute to neural representations of space in the hippocampus. Using in vivo two-photon calcium imaging we recorded neuronal activity from three different areas of the hippocampus while animals were head-fixed under the microscope on a treadmill. We found that mice that were previously housed in an enriched environment, which triggers an increase in neurogenesis, had increased spatial information content in the hippocampal dentate gyrus during novel context exposure. Ablating adult neurogenesis by prior focal irradiation of the hippocampus blocked the effect of enrichment and lowered spatial information content, as did the chemogenetic silencing of adult-born neurons. Both ablating neurogenesis and silencing adult-born neurons decreased the calcium activity rates of dentate gyrus neurons, resulting in a decreased amplitude of place-specific responses. These findings contrast previous studies that suggested a predominantly inhibitory action for adult-born neurons. Additionally, animals with prior exposure to an enriched environment exhibited an increase in spatial information content the CA1 region of the hippocampus in animals exposed to an enriched environment. Ablating adult neurogenesis by prior focal irradiation resulted in a decrease in spatial information content potentially driven by an overall increase in noise in the tuning curves of pyramidal cells. Although we observed no change in the amplitude of the place specific responses in animals with prior exposure to enriched environment, we did find a decrease in the width of these responses. The increase in overall noise could indicate additional mechanisms at play such as direct inputs from the entorhinal cortex influencing the overall firing patterns of CA1. In irradiated animals with prior exposure to an enriched environment, mossy cells showed a decrease in spatial information content when compared to their non-irradiated counterparts. Spatial tuning was also reduced as observed by a reduction in both unimodal and bimodal place-specific responses. Conversely, animals housed in regular cage conditions with prior exposure to focal irradiation exhibited an increase spatial information content and complexity of the place-specific responses. These results suggest the role of mossy cells in the formation of neuronal representations of space may be partially dependent on adult neurogenesis and plasticity mechanisms induced by environmental enrichment. Overall, we propose that adult neurogenesis improves neural representations of space by modulating the shape of the tuning curves and therefore improving the ability of dentate gyrus neurons to tune to spatial features resulting in increased spatial information content in the hippocampus. These findings contribute to our understanding of how adult neurogenesis positively influences spatial learning and memory by elucidating the mechanisms by which adult-born neurons facilitate the formation of neuronal representations of space in the hippocampus. |
URI / Handle: | https://hdl.handle.net/20.500.12381/3608 |
Financiadores: | Agencia Nacional de Investigación e Innovación Comision Fulbright Uruguay Albert Einstein College of Medicine |
Identificador ANII: | POS_FUL_2016_1_1005350 |
Nivel de Acceso: | Acceso abierto |
Licencia CC: | Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND) |
Aparece en las colecciones: | Publicaciones de ANII |
Archivos en este ítem:
archivo | Descripción | Tamaño | Formato | |
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Thesis - Maria Frechou.pdf | 22.06 MB | Adobe PDF | Descargar |
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Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)