Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors
A major intracellular messenger implicated in synaptic plasticity and cognitive functions both in health and disease is cyclic GMP (cGMP). Utilizing a photoactivatable guanylyl cyclase (BlgC) actuator to increase cGMP in dentate granule neurons of the hippocampus by light, we studied the effects of...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1479360/full |
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| author | Jelena Borovac Jelena Borovac Jelena Borovac Jayant Rai Jayant Rai Megan Valencia Megan Valencia Hang Li John Georgiou Graham L. Collingridge Graham L. Collingridge Graham L. Collingridge Keizo Takao Keizo Takao Keizo Takao Kenichi Okamoto Kenichi Okamoto |
| author_facet | Jelena Borovac Jelena Borovac Jelena Borovac Jayant Rai Jayant Rai Megan Valencia Megan Valencia Hang Li John Georgiou Graham L. Collingridge Graham L. Collingridge Graham L. Collingridge Keizo Takao Keizo Takao Keizo Takao Kenichi Okamoto Kenichi Okamoto |
| author_sort | Jelena Borovac |
| collection | DOAJ |
| description | A major intracellular messenger implicated in synaptic plasticity and cognitive functions both in health and disease is cyclic GMP (cGMP). Utilizing a photoactivatable guanylyl cyclase (BlgC) actuator to increase cGMP in dentate granule neurons of the hippocampus by light, we studied the effects of spatiotemporal cGMP elevations in synaptic and cognitive functions. At medial perforant path to dentate gyrus (MPP-DG) synapses, we found enhanced long-term potentiation (LTP) of synaptic responses when postsynaptic cGMP was elevated during the induction period. Basal synaptic transmission and the paired-pulse ratio were unaffected, suggesting the cGMP effect on LTP was postsynaptic in origin. In behaving mice implanted with a fiber optic and wireless LED device, their performance following DG photoactivation (5–10 min) was studied in a variety of behavioral tasks. There were enhancements in reference memory and social behavior within tens of minutes following DG BlgC photoactivation, and with time (hours), an anxiogenic effect developed. Thus, postsynaptic cGMP elevations, specifically in the DG and specifically during conditions that evoke synaptic plasticity or during experience, are able to rapidly modify synaptic strength and behavioral responses, respectively. The optogenetics technology and new roles for cGMP in the DG may have applications in brain disorders that are impacted by dysregulated cGMP signaling, such as Alzheimer’s disease. |
| format | Article |
| id | doaj-art-ad5fc69ea26d48698e6b09b7c53c33d6 |
| institution | OA Journals |
| issn | 1662-5099 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj-art-ad5fc69ea26d48698e6b09b7c53c33d62025-08-20T02:27:31ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-11-011710.3389/fnmol.2024.14793601479360Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviorsJelena Borovac0Jelena Borovac1Jelena Borovac2Jayant Rai3Jayant Rai4Megan Valencia5Megan Valencia6Hang Li7John Georgiou8Graham L. Collingridge9Graham L. Collingridge10Graham L. Collingridge11Keizo Takao12Keizo Takao13Keizo Takao14Kenichi Okamoto15Kenichi Okamoto16Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaDepartment of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaDepartment of Behavioral Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaDepartment of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaDepartment of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaTANZ Centre for Research in Neurodegenerative Diseases (CRND), University of Toronto, Toronto, ON, CanadaDepartment of Behavioral Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanDepartment of Behavioral Physiology, Faculty of Medicine, University of Toyama, Toyama, JapanResearch Centre for Idling Brain Science, University of Toyama, Toyama, JapanLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, CanadaDepartment of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaA major intracellular messenger implicated in synaptic plasticity and cognitive functions both in health and disease is cyclic GMP (cGMP). Utilizing a photoactivatable guanylyl cyclase (BlgC) actuator to increase cGMP in dentate granule neurons of the hippocampus by light, we studied the effects of spatiotemporal cGMP elevations in synaptic and cognitive functions. At medial perforant path to dentate gyrus (MPP-DG) synapses, we found enhanced long-term potentiation (LTP) of synaptic responses when postsynaptic cGMP was elevated during the induction period. Basal synaptic transmission and the paired-pulse ratio were unaffected, suggesting the cGMP effect on LTP was postsynaptic in origin. In behaving mice implanted with a fiber optic and wireless LED device, their performance following DG photoactivation (5–10 min) was studied in a variety of behavioral tasks. There were enhancements in reference memory and social behavior within tens of minutes following DG BlgC photoactivation, and with time (hours), an anxiogenic effect developed. Thus, postsynaptic cGMP elevations, specifically in the DG and specifically during conditions that evoke synaptic plasticity or during experience, are able to rapidly modify synaptic strength and behavioral responses, respectively. The optogenetics technology and new roles for cGMP in the DG may have applications in brain disorders that are impacted by dysregulated cGMP signaling, such as Alzheimer’s disease.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1479360/fullcGMPoptogeneticselectrophysiologylong-term potentiationsynaptic plasticitymemory |
| spellingShingle | Jelena Borovac Jelena Borovac Jelena Borovac Jayant Rai Jayant Rai Megan Valencia Megan Valencia Hang Li John Georgiou Graham L. Collingridge Graham L. Collingridge Graham L. Collingridge Keizo Takao Keizo Takao Keizo Takao Kenichi Okamoto Kenichi Okamoto Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors Frontiers in Molecular Neuroscience cGMP optogenetics electrophysiology long-term potentiation synaptic plasticity memory |
| title | Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors |
| title_full | Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors |
| title_fullStr | Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors |
| title_full_unstemmed | Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors |
| title_short | Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors |
| title_sort | optogenetic elevation of postsynaptic cgmp in the hippocampal dentate gyrus enhances ltp and modifies mouse behaviors |
| topic | cGMP optogenetics electrophysiology long-term potentiation synaptic plasticity memory |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1479360/full |
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