{"id":{"repo_id":"catania","oai_identifier":"oai:www.iris.unict.it:20.500.11769/583566"},"canonical_url":"https://search.dev.ndltd.org/etd/catania/oai:www.iris.unict.it:20.500.11769/583566","repository":{"repo_id":"catania","name":"Università degli Studi di Catania","base_url":"https://www.iris.unict.it/oai/request"},"display":{"title":"Cell-type specific CB1 receptor modulation of hippocampal synaptic plasticity and memory","abstract":"The endocannabinoid system is a major brain modulatory system that controls memory and learning mainly via the cannabinoid receptor type 1 (CB1)-dependent regulation of neuronal and glial activity. In the hippocampus, bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. CB1 receptors have been shown to be present in the astrocytes and to mediate the disruptive effects of cannabinoids in synaptic plasticity and working memory. Yet, it is not currently known the role of this receptor in the physiological modulation of memory processes. Also, previous studies have shown that CB1 receptors expressed in dopamine D1 receptor-expressing cells are involved in the modulation of hippocampal-dependent aversive memories. However, their involvement in the modulation of non-aversive long-term memory formation and synaptic plasticity is presently unknown. In this thesis, I aimed at identifying the cellular and molecular mechanisms by which specific CB1 receptors in distinct brain neuronal and glial populations contribute to the physiological modulation of synaptic plasticity and learning and memory. For this aim we used conditional genetic mutant mice lacking CB1 receptors specifically in astrocytes or in D1-positive cells. By coupling these genetic mouse models with behavioral, pharmacological, and in vitro and in vivo electrophysiological approaches, we dissected the role of these CB1 receptors in the formation of memory. First, we show that astroglial CB1 receptors in the hippocampus control long-term potentiation (LTP) of CA3-CA1 synaptic transmission and long-term recognition memory. By allowing physiological availability of D-serine at NMDA receptors via gliotransmission, astrocytes are important elements controlling glia-neuron interactions that underlie synaptic plasticity and memory functions. The data show that astroglial CB1 receptors control plasticity and memory by regulating the synaptic availability of D-serine at NMDA receptors. Second, we show that CB1 receptors D1-positive cells control the consolidation, but not acquisition, of new memories and the enhancement of LTP induced by learning, showing that specific subpopulations CB1 receptor-expressing cells differentially modulate these processes. Overall, by showing that the endocannabinoid system in astrocytes is an important modulator of learning and memory and by suggesting that CB1 receptors in D1-positive cells are important for specific components of memory formation, we provide functional evidence for the complex cell type-dependent regulation of long-term recognition memory by the CB1 receptors.","abstract_html":"The endocannabinoid system is a major brain modulatory system that controls memory and learning mainly via the cannabinoid receptor type 1 (CB1)-dependent regulation of neuronal and glial activity. In the hippocampus, bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. CB1 receptors have been shown to be present in the astrocytes and to mediate the disruptive effects of cannabinoids in synaptic plasticity and working memory. Yet, it is not currently known the role of this receptor in the physiological modulation of memory processes. Also, previous studies have shown that CB1 receptors expressed in dopamine D1 receptor-expressing cells are involved in the modulation of hippocampal-dependent aversive memories. However, their involvement in the modulation of non-aversive long-term memory formation and synaptic plasticity is presently unknown. In this thesis, I aimed at identifying the cellular and molecular mechanisms by which specific CB1 receptors in distinct brain neuronal and glial populations contribute to the physiological modulation of synaptic plasticity and learning and memory. For this aim we used conditional genetic mutant mice lacking CB1 receptors specifically in astrocytes or in D1-positive cells. By coupling these genetic mouse models with behavioral, pharmacological, and in vitro and in vivo electrophysiological approaches, we dissected the role of these CB1 receptors in the formation of memory. First, we show that astroglial CB1 receptors in the hippocampus control long-term potentiation (LTP) of CA3-CA1 synaptic transmission and long-term recognition memory. By allowing physiological availability of D-serine at NMDA receptors via gliotransmission, astrocytes are important elements controlling glia-neuron interactions that underlie synaptic plasticity and memory functions. The data show that astroglial CB1 receptors control plasticity and memory by regulating the synaptic availability of D-serine at NMDA receptors. Second, we show that CB1 receptors D1-positive cells control the consolidation, but not acquisition, of new memories and the enhancement of LTP induced by learning, showing that specific subpopulations CB1 receptor-expressing cells differentially modulate these processes. Overall, by showing that the endocannabinoid system in astrocytes is an important modulator of learning and memory and by suggesting that CB1 receptors in D1-positive cells are important for specific components of memory formation, we provide functional evidence for the complex cell type-dependent regulation of long-term recognition memory by the CB1 receptors.","abstract_has_math":false,"creators":["JOSE FERNANDO, OLIVEIRA DA CRUZ"],"institution":"Università degli studi di Catania","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["DRAGO, Filippo","SALOMONE, Salvatore"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-11-30","date_published":"2017-11-30","updated_at":"2026-07-24T01:35:15Z","subjects":["CB1 receptors, D1 receptors, astrocytes, D-serine, LTP, Memory, Récepteurs CB1, récepteurs D1, astrocytes, D-sérine, PLT, Mémoire"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess","license:PUBBLICO - Pubblico con Copyright","license uri:iris.PUB02"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.11769/583566","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["JOSE FERNANDO, OLIVEIRA DA CRUZ","DRAGO, Filippo","SALOMONE, Salvatore"]},{"key":"dc:creator","label":"Author","values":["JOSE FERNANDO, OLIVEIRA DA CRUZ"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2017-11-30"]},{"key":"dc:publisher","label":"Institution","values":["Università degli studi di Catania","place:Catania"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["CB1 receptors, D1 receptors, astrocytes, D-serine, LTP, Memory, Récepteurs CB1, récepteurs D1, astrocytes, D-sérine, PLT, Mémoire"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess","license:PUBBLICO - Pubblico con Copyright","license uri:iris.PUB02"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/20.500.11769/583566"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The endocannabinoid system is a major brain modulatory system that controls memory and learning mainly via the cannabinoid receptor type 1 (CB1)-dependent regulation of neuronal and glial activity. In the hippocampus, bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. CB1 receptors have been shown to be present in the astrocytes and to mediate the disruptive effects of cannabinoids in synaptic plasticity and working memory. Yet, it is not currently known the role of this receptor in the physiological modulation of memory processes. Also, previous studies have shown that CB1 receptors expressed in dopamine D1 receptor-expressing cells are involved in the modulation of hippocampal-dependent aversive memories. However, their involvement in the modulation of non-aversive long-term memory formation and synaptic plasticity is presently unknown. In this thesis, I aimed at identifying the cellular and molecular mechanisms by which specific CB1 receptors in distinct brain neuronal and glial populations contribute to the physiological modulation of synaptic plasticity and learning and memory. For this aim we used conditional genetic mutant mice lacking CB1 receptors specifically in astrocytes or in D1-positive cells. By coupling these genetic mouse models with behavioral, pharmacological, and in vitro and in vivo electrophysiological approaches, we dissected the role of these CB1 receptors in the formation of memory. First, we show that astroglial CB1 receptors in the hippocampus control long-term potentiation (LTP) of CA3-CA1 synaptic transmission and long-term recognition memory. By allowing physiological availability of D-serine at NMDA receptors via gliotransmission, astrocytes are important elements controlling glia-neuron interactions that underlie synaptic plasticity and memory functions. The data show that astroglial CB1 receptors control plasticity and memory by regulating the synaptic availability of D-serine at NMDA receptors. Second, we show that CB1 receptors D1-positive cells control the consolidation, but not acquisition, of new memories and the enhancement of LTP induced by learning, showing that specific subpopulations CB1 receptor-expressing cells differentially modulate these processes. Overall, by showing that the endocannabinoid system in astrocytes is an important modulator of learning and memory and by suggesting that CB1 receptors in D1-positive cells are important for specific components of memory formation, we provide functional evidence for the complex cell type-dependent regulation of long-term recognition memory by the CB1 receptors.","Le système endocannabinoïde est un système neuromodulateur majeur du cerveau. Ainsi, il contrôle la mémoire et l apprentissage, et ce, principalement par l'intermédiaire des récepteurs aux cannabinoïdes de type 1 (CB1) qui régulent de manière fine les activités neuronales et gliales. Dans l hippocampe, une communication bidirectionnelle entre neurones et astrocytes modèle la plasticité synaptique et le comportement. Il a été rapporté que les effets disruptifs des cannabinoïdes sur la plasticité synaptique et la mémoire de travail sont dépendants de récepteurs CB1 présents dans les astrocytes. Cependant, le rôle de ce récepteur dans la modulation physiologique des processus mnésiques n est pas encore connu. De précédentes études ont également montré que les récepteurs CB1 exprimés dans les cellules hébergeant le récepteur dopaminergique D1 sont impliqués dans la modulation hippocampique de la mémoire associée aux évènements aversifs. Toutefois, leur implication dans la modulation de la formation de la mémoire associée à des évènements non aversifs ainsi que dans la plasticité synaptique sous-jacente reste encore inconnue. Dans cette thèse, mon objectif était d identifier les mécanismes cellulaires et moléculaires par lesquels des populations distinctes de récepteurs CB1 dans des populations gliales et des régions cérébrales bien définies contribuent à la modulation physiologique de la plasticité synaptique, de l apprentissage et de la mémoire. Pour ce faire, nous avons utilisé des souris mutantes conditionnelles dans lesquelles le récepteur CB1 a été rendu silencieux sélectivement dans les astrocytes ou dans les cellules exprimant le récepteur D1. En couplant ces modèles génétiques murins avec des approches comportementales, pharmacologiques et électrophysiologiques in vitro et in vivo, nous avons disséqué le rôle de ces populations de récepteurs CB1 dans la formation de la mémoire. Tout d abord, nous avons montré que les récepteurs CB1 astrogliaux dans l hippocampe contrôlaient la potentialisation à long terme (PLT) de la transmission synaptique CA3-CA1 et la mémoire de reconnaissance à long terme. En contrôlant, via la gliotransmission, la disponibilité effective de D-sérine aux récepteurs NMDA, les astrocytes sont des éléments importants contrôlant les interactions glie-neurones qui sous-tendent la plasticité synaptique et les fonctions mnésiques. Les données obtenues montrent que les récepteurs CB1 astrogliaux contrôlent la plasticité et la mémoire en régulant la disponibilité synaptique de la D-sérine aux récepteurs NMDA. Deuxièmement, nous avons montré que les récepteurs CB1 dans les cellules exprimant le récepteur D1 contrôlaient la consolidation, mais pas l acquisition, de nouveau souvenirs et l augmentation de la PLT induite par l apprentissage. Ces résultats indiquent que des populations spécifiques de cellules exprimant le récepteur CB1 modulent ces processus de manière différentielle. En conclusion, ces travaux démontrent que le système endocannabinoïde dans les astrocytes est un important modulateur de l apprentissage et de la mémoire alors que les récepteurs CB1 dans les cellules exprimant le récepteur D1 semblent importants pour des composantes spécifiques de la formation de la mémoire. Prise dans son ensemble, cette thèse apporte des preuves fonctionnelles quant à la régulation complexe de la mémoire de reconnaissance à long-terme par des populations distinctes de récepteurs CB1."]},{"key":"dc:title","label":"Title","values":["Cell-type specific CB1 receptor modulation of hippocampal synaptic plasticity and memory"]}]}],"canonical_facts":{"dc:contributor":["JOSE FERNANDO, OLIVEIRA DA CRUZ","DRAGO, Filippo","SALOMONE, Salvatore"],"dc:creator":["JOSE FERNANDO, OLIVEIRA DA CRUZ"],"dc:date":["2017-11-30"],"dc:description":["The endocannabinoid system is a major brain modulatory system that controls memory and learning mainly via the cannabinoid receptor type 1 (CB1)-dependent regulation of neuronal and glial activity. In the hippocampus, bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. CB1 receptors have been shown to be present in the astrocytes and to mediate the disruptive effects of cannabinoids in synaptic plasticity and working memory. Yet, it is not currently known the role of this receptor in the physiological modulation of memory processes. Also, previous studies have shown that CB1 receptors expressed in dopamine D1 receptor-expressing cells are involved in the modulation of hippocampal-dependent aversive memories. However, their involvement in the modulation of non-aversive long-term memory formation and synaptic plasticity is presently unknown. In this thesis, I aimed at identifying the cellular and molecular mechanisms by which specific CB1 receptors in distinct brain neuronal and glial populations contribute to the physiological modulation of synaptic plasticity and learning and memory. For this aim we used conditional genetic mutant mice lacking CB1 receptors specifically in astrocytes or in D1-positive cells. By coupling these genetic mouse models with behavioral, pharmacological, and in vitro and in vivo electrophysiological approaches, we dissected the role of these CB1 receptors in the formation of memory. First, we show that astroglial CB1 receptors in the hippocampus control long-term potentiation (LTP) of CA3-CA1 synaptic transmission and long-term recognition memory. By allowing physiological availability of D-serine at NMDA receptors via gliotransmission, astrocytes are important elements controlling glia-neuron interactions that underlie synaptic plasticity and memory functions. The data show that astroglial CB1 receptors control plasticity and memory by regulating the synaptic availability of D-serine at NMDA receptors. Second, we show that CB1 receptors D1-positive cells control the consolidation, but not acquisition, of new memories and the enhancement of LTP induced by learning, showing that specific subpopulations CB1 receptor-expressing cells differentially modulate these processes. Overall, by showing that the endocannabinoid system in astrocytes is an important modulator of learning and memory and by suggesting that CB1 receptors in D1-positive cells are important for specific components of memory formation, we provide functional evidence for the complex cell type-dependent regulation of long-term recognition memory by the CB1 receptors.","Le système endocannabinoïde est un système neuromodulateur majeur du cerveau. Ainsi, il contrôle la mémoire et l apprentissage, et ce, principalement par l'intermédiaire des récepteurs aux cannabinoïdes de type 1 (CB1) qui régulent de manière fine les activités neuronales et gliales. Dans l hippocampe, une communication bidirectionnelle entre neurones et astrocytes modèle la plasticité synaptique et le comportement. Il a été rapporté que les effets disruptifs des cannabinoïdes sur la plasticité synaptique et la mémoire de travail sont dépendants de récepteurs CB1 présents dans les astrocytes. Cependant, le rôle de ce récepteur dans la modulation physiologique des processus mnésiques n est pas encore connu. De précédentes études ont également montré que les récepteurs CB1 exprimés dans les cellules hébergeant le récepteur dopaminergique D1 sont impliqués dans la modulation hippocampique de la mémoire associée aux évènements aversifs. Toutefois, leur implication dans la modulation de la formation de la mémoire associée à des évènements non aversifs ainsi que dans la plasticité synaptique sous-jacente reste encore inconnue. Dans cette thèse, mon objectif était d identifier les mécanismes cellulaires et moléculaires par lesquels des populations distinctes de récepteurs CB1 dans des populations gliales et des régions cérébrales bien définies contribuent à la modulation physiologique de la plasticité synaptique, de l apprentissage et de la mémoire. Pour ce faire, nous avons utilisé des souris mutantes conditionnelles dans lesquelles le récepteur CB1 a été rendu silencieux sélectivement dans les astrocytes ou dans les cellules exprimant le récepteur D1. En couplant ces modèles génétiques murins avec des approches comportementales, pharmacologiques et électrophysiologiques in vitro et in vivo, nous avons disséqué le rôle de ces populations de récepteurs CB1 dans la formation de la mémoire. Tout d abord, nous avons montré que les récepteurs CB1 astrogliaux dans l hippocampe contrôlaient la potentialisation à long terme (PLT) de la transmission synaptique CA3-CA1 et la mémoire de reconnaissance à long terme. En contrôlant, via la gliotransmission, la disponibilité effective de D-sérine aux récepteurs NMDA, les astrocytes sont des éléments importants contrôlant les interactions glie-neurones qui sous-tendent la plasticité synaptique et les fonctions mnésiques. Les données obtenues montrent que les récepteurs CB1 astrogliaux contrôlent la plasticité et la mémoire en régulant la disponibilité synaptique de la D-sérine aux récepteurs NMDA. Deuxièmement, nous avons montré que les récepteurs CB1 dans les cellules exprimant le récepteur D1 contrôlaient la consolidation, mais pas l acquisition, de nouveau souvenirs et l augmentation de la PLT induite par l apprentissage. Ces résultats indiquent que des populations spécifiques de cellules exprimant le récepteur CB1 modulent ces processus de manière différentielle. En conclusion, ces travaux démontrent que le système endocannabinoïde dans les astrocytes est un important modulateur de l apprentissage et de la mémoire alors que les récepteurs CB1 dans les cellules exprimant le récepteur D1 semblent importants pour des composantes spécifiques de la formation de la mémoire. Prise dans son ensemble, cette thèse apporte des preuves fonctionnelles quant à la régulation complexe de la mémoire de reconnaissance à long-terme par des populations distinctes de récepteurs CB1."],"dc:identifier":["https://hdl.handle.net/20.500.11769/583566"],"dc:language":["eng"],"dc:publisher":["Università degli studi di Catania","place:Catania"],"dc:rights":["info:eu-repo/semantics/openAccess","license:PUBBLICO - Pubblico con Copyright","license uri:iris.PUB02"],"dc:subject":["CB1 receptors, D1 receptors, astrocytes, D-serine, LTP, Memory, Récepteurs CB1, récepteurs D1, astrocytes, D-sérine, PLT, Mémoire"],"dc:title":["Cell-type specific CB1 receptor modulation of hippocampal synaptic plasticity and memory"],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-24T01:35:15Z"}