Role of Adult-Born Neurons in Hippocampal Representations of Space

Frechou Schandy, Maria Agustina

Supervisor(es): Goncalves, J. Tiago

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.


Detalles Bibliográficos
2023
Agencia Nacional de Investigación e Innovación
Comision Fulbright Uruguay
Albert Einstein College of Medicine
Neurogenesis
Giro dentado
Microscopia de 2 fotones
Memoria espacial
Ciencias Médicas y de la Salud
Medicina Básica
Neurociencias
Inglés
Agencia Nacional de Investigación e Innovación
REDI
https://hdl.handle.net/20.500.12381/3608
Acceso abierto
Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)
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author Frechou Schandy, Maria Agustina
author_facet Frechou Schandy, Maria Agustina
author_role author
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bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
bitstream.url.fl_str_mv https://redi.anii.org.uy/jspui/bitstream/20.500.12381/3608/2/license.txt
https://redi.anii.org.uy/jspui/bitstream/20.500.12381/3608/1/Thesis%20-%20Maria%20Frechou.pdf
collection REDI
dc.creator.advisor.none.fl_str_mv Goncalves, J. Tiago
dc.creator.none.fl_str_mv Frechou Schandy, Maria Agustina
dc.date.accessioned.none.fl_str_mv 2024-08-28T17:09:36Z
dc.date.available.none.fl_str_mv 2024-08-28T17:09:36Z
dc.date.issued.none.fl_str_mv 2023-09-29
dc.description.abstract.none.fl_txt_mv 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.
dc.description.sponsorship.none.fl_txt_mv Agencia Nacional de Investigación e Innovación
Comision Fulbright Uruguay
Albert Einstein College of Medicine
dc.identifier.anii.es.fl_str_mv POS_FUL_2016_1_1005350
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12381/3608
dc.language.iso.none.fl_str_mv eng
dc.publisher.es.fl_str_mv Albert Einstein College of Medicine
dc.rights.*.fl_str_mv Acceso abierto
dc.rights.license.none.fl_str_mv Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:REDI
instname:Agencia Nacional de Investigación e Innovación
instacron:Agencia Nacional de Investigación e Innovación
dc.subject.anii.none.fl_str_mv Ciencias Médicas y de la Salud
Medicina Básica
Neurociencias
dc.subject.es.fl_str_mv Neurogenesis
Giro dentado
Microscopia de 2 fotones
Memoria espacial
dc.title.none.fl_str_mv Role of Adult-Born Neurons in Hippocampal Representations of Space
dc.type.es.fl_str_mv Tesis de doctorado
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.version.es.fl_str_mv Publicado
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description 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.
eu_rights_str_mv openAccess
format doctoralThesis
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repository.mail.fl_str_mv jmaldini@anii.org.uy
repository.name.fl_str_mv REDI - Agencia Nacional de Investigación e Innovación
repository_id_str 9421
rights_invalid_str_mv Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)
Acceso abierto
spelling Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)Acceso abiertoinfo:eu-repo/semantics/openAccess2024-08-28T17:09:36Z2024-08-28T17:09:36Z2023-09-29https://hdl.handle.net/20.500.12381/3608POS_FUL_2016_1_1005350Adult 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.Agencia Nacional de Investigación e InnovaciónComision Fulbright UruguayAlbert Einstein College of MedicineengAlbert Einstein College of MedicineNeurogenesisGiro dentadoMicroscopia de 2 fotonesMemoria espacialCiencias Médicas y de la SaludMedicina BásicaNeurocienciasRole of Adult-Born Neurons in Hippocampal Representations of SpaceTesis de doctoradoPublicadoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis//Ciencias Médicas y de la Salud/Medicina Básica/Neurocienciasreponame:REDIinstname:Agencia Nacional de Investigación e Innovacióninstacron:Agencia Nacional de Investigación e InnovaciónFrechou Schandy, Maria AgustinaGoncalves, J. TiagoLICENSElicense.txtlicense.txttext/plain; charset=utf-84967https://redi.anii.org.uy/jspui/bitstream/20.500.12381/3608/2/license.txta4ce09f01b5dd771727aa05c73851623MD52ORIGINALThesis - Maria Frechou.pdfThesis - Maria Frechou.pdfapplication/pdf22591873https://redi.anii.org.uy/jspui/bitstream/20.500.12381/3608/1/Thesis%20-%20Maria%20Frechou.pdff91bde345c3c3994f0ccf8d966428586MD5120.500.12381/36082024-08-28 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- Agencia Nacional de Investigación e Innovaciónfalse
spellingShingle Role of Adult-Born Neurons in Hippocampal Representations of Space
Frechou Schandy, Maria Agustina
Neurogenesis
Giro dentado
Microscopia de 2 fotones
Memoria espacial
Ciencias Médicas y de la Salud
Medicina Básica
Neurociencias
status_str publishedVersion
title Role of Adult-Born Neurons in Hippocampal Representations of Space
title_full Role of Adult-Born Neurons in Hippocampal Representations of Space
title_fullStr Role of Adult-Born Neurons in Hippocampal Representations of Space
title_full_unstemmed Role of Adult-Born Neurons in Hippocampal Representations of Space
title_short Role of Adult-Born Neurons in Hippocampal Representations of Space
title_sort Role of Adult-Born Neurons in Hippocampal Representations of Space
topic Neurogenesis
Giro dentado
Microscopia de 2 fotones
Memoria espacial
Ciencias Médicas y de la Salud
Medicina Básica
Neurociencias
url https://hdl.handle.net/20.500.12381/3608