Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics

[eng] Synapses are the contact sites where the transfer of information from the presynaptic to the postsynaptic site occurs. Correct processing of information requires that synapses continuously adapt their properties to an ever-changing environment. Here, we describe novel aspects that help underst...

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Detalles Bibliográficos
Autor: Velasco Domínguez, Cecilia
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/186815
Acceso en línea:https://hdl.handle.net/2445/186815
http://hdl.handle.net/10803/674605
Access Level:acceso abierto
Palabra clave:Neurologia
Sinapsi
Neurotransmissió
Neurofisiologia
Neurology
Synapses
Neural transmission
Neurophysiology
id ES_e5bde32fdf4c2c6b35dfd81f19e394ee
oai_identifier_str oai:diposit.ub.edu:2445/186815
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
title Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
spellingShingle Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
Velasco Domínguez, Cecilia
Neurologia
Sinapsi
Neurotransmissió
Neurofisiologia
Neurology
Synapses
Neural transmission
Neurophysiology
title_short Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
title_full Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
title_fullStr Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
title_full_unstemmed Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
title_sort Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamics
dc.creator.none.fl_str_mv Velasco Domínguez, Cecilia
author Velasco Domínguez, Cecilia
author_facet Velasco Domínguez, Cecilia
author_role author
dc.contributor.none.fl_str_mv Llobet Berenguer, Artur, 1972-
Terni, Beatrice
Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental
dc.subject.none.fl_str_mv Neurologia
Sinapsi
Neurotransmissió
Neurofisiologia
Neurology
Synapses
Neural transmission
Neurophysiology
topic Neurologia
Sinapsi
Neurotransmissió
Neurofisiologia
Neurology
Synapses
Neural transmission
Neurophysiology
description [eng] Synapses are the contact sites where the transfer of information from the presynaptic to the postsynaptic site occurs. Correct processing of information requires that synapses continuously adapt their properties to an ever-changing environment. Here, we describe novel aspects that help understand the function of presynaptic terminals in the context of a simple neuronal network. The exuberant number of synaptic contacts formed during the development of the nervous system is selectively refined by a process of synapse elimination. In the current thesis we have exploited the action of peptide p4.2, a 20 amino acid fragment located in the C-terminus of the glial secreted protein SPARC, which promotes synapse elimination in an autaptic circuit. We found that neurons forming autaptic synapses sense and compensate for synapse elimination by activating a mechanism of presynaptic homeostatic plasticity driven by presynaptic potentiation and rapid assembly of new synaptic contacts. Both actions occur concomitantly, indicating that the formation of novel synapses is associated to an overall increase in presynaptic calcium influx. To further investigate the molecular mechanisms underlying this compensatory response, we moved our interests to the participation of microtubules in the maintenance of synaptic connectivity and synaptic strength. This question could only be addressed by gaining a better understanding of the participation of microtubules in presynaptic terminal function. By providing ultrastructural, morphological, and physiological evidence we have shown that microtubule plus-ends transiently invade presynaptic boutons and that microtubule instability is directly involved in the regulation of spontaneous neurotransmitter release probability. Microtubule polymerization is also important to postsynaptic function, indicating microtubule dynamics might be involved in forms of postsynaptic plasticity. Altogether, the development of this project has allowed to identify yet unknown mechanisms key for better understanding the cell biology of presynaptic terminals. These findings should not only be considered in the context of a simple neuronal network, chosen because of its unique experimental possibilities, but as fundamental neuronal properties. Yet, future research in complex systems are required to further validate our findings.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/186815
http://hdl.handle.net/10803/674605
url https://hdl.handle.net/2445/186815
http://hdl.handle.net/10803/674605
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Velasco Domínguez, Cecilia, 2022
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Velasco Domínguez, Cecilia, 2022
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Departament - Patologia i Terapèutica Experimental
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422706416418816
spelling Synaptic transmission in autaptic circuits: presynaptic homeostatic plasticity and microtubule dynamicsVelasco Domínguez, CeciliaNeurologiaSinapsiNeurotransmissióNeurofisiologiaNeurologySynapsesNeural transmissionNeurophysiology[eng] Synapses are the contact sites where the transfer of information from the presynaptic to the postsynaptic site occurs. Correct processing of information requires that synapses continuously adapt their properties to an ever-changing environment. Here, we describe novel aspects that help understand the function of presynaptic terminals in the context of a simple neuronal network. The exuberant number of synaptic contacts formed during the development of the nervous system is selectively refined by a process of synapse elimination. In the current thesis we have exploited the action of peptide p4.2, a 20 amino acid fragment located in the C-terminus of the glial secreted protein SPARC, which promotes synapse elimination in an autaptic circuit. We found that neurons forming autaptic synapses sense and compensate for synapse elimination by activating a mechanism of presynaptic homeostatic plasticity driven by presynaptic potentiation and rapid assembly of new synaptic contacts. Both actions occur concomitantly, indicating that the formation of novel synapses is associated to an overall increase in presynaptic calcium influx. To further investigate the molecular mechanisms underlying this compensatory response, we moved our interests to the participation of microtubules in the maintenance of synaptic connectivity and synaptic strength. This question could only be addressed by gaining a better understanding of the participation of microtubules in presynaptic terminal function. By providing ultrastructural, morphological, and physiological evidence we have shown that microtubule plus-ends transiently invade presynaptic boutons and that microtubule instability is directly involved in the regulation of spontaneous neurotransmitter release probability. Microtubule polymerization is also important to postsynaptic function, indicating microtubule dynamics might be involved in forms of postsynaptic plasticity. Altogether, the development of this project has allowed to identify yet unknown mechanisms key for better understanding the cell biology of presynaptic terminals. These findings should not only be considered in the context of a simple neuronal network, chosen because of its unique experimental possibilities, but as fundamental neuronal properties. Yet, future research in complex systems are required to further validate our findings.[spa] Las sinapsis son los sitios de contacto donde ocurre la transferencia de información desde el terminal presináptico al postsináptico. El correcto procesamiento de información requiere que las sinapsis adapten continuamente sus propiedades bajo un entorno de constante cambio. En esta tesis describimos aspectos novedosos que ayudan a comprender la función de los terminales presinápticos en el contexto de una red neuronal simple. El número exuberante de contactos sinápticos formados durante el desarrollo del sistema nervioso se refina selectivamente mediante un proceso de eliminación sináptica. En la presente tesis hemos explotado la acción del péptido p4.2, un fragmento de 20 aminoácidos situado en el extremo C-terminal de la proteína de secreción glial SPARC, que promueve la eliminación de sinapsis en un circuito autáptico. Hemos descubierto que las neuronas que forman sinapsis autápticas detectan y compensan la eliminación sináptica activando un mecanismo de plasticidad homeostática presináptica impulsado por la potenciación presináptica y el rápido ensamblaje de nuevos contactos sinápticos. Ambas acciones ocurren de manera concomitante, lo que indica que la formación de nuevas sinapsis está asociada con un aumento general en el flujo de entrada de calcio presináptico. Para investigar más a fondo los mecanismos moleculares que subyacen a esta respuesta compensatoria, trasladamos nuestro foco de investigación a la participación de los microtúbulos en el mantenimiento de la conectividad y fuerza sináptica. Proporcionando evidencia ultraestructural, morfológica y fisiológica, hemos demostrado que los extremos positivos de los microtúbulos invaden transitoriamente los botones presinápticos y que la inestabilidad de los microtúbulos está directamente involucrada en la regulación de la probabilidad de liberación espontánea de neurotransmisores. La polimerización de microtúbulos también es importante para la función postsináptica, lo que indica que la dinámica de los microtúbulos podría estar involucrada en formas de plasticidad postsináptica. El desarrollo de este proyecto ha permitido identificar mecanismos aún desconocidos que son clave para entender la biología celular de los terminales presinápticos. Estos hallazgos no solo deben considerarse en el contexto de una red neuronal simple, elegida por sus posibilidades experimentales únicas, sino como propiedades neuronales fundamentales. Sin embargo, futuras investigaciones en sistemas complejos son necesarias para validar nuestros hallazgos.Universitat de BarcelonaLlobet Berenguer, Artur, 1972-Terni, BeatriceUniversitat de Barcelona. Departament de Patologia i Terapèutica Experimental2022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/186815http://hdl.handle.net/10803/674605Tesis Doctorals - Departament - Patologia i Terapèutica Experimentalreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Velasco Domínguez, Cecilia, 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1868152026-05-27T06:46:51Z
score 15,300719

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