Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus
Long-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2023-04-01
|
Series: | Frontiers in Cellular Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1068472/full |
_version_ | 1797852181427126272 |
---|---|
author | Stefano Lutzu Karina Alviña Nagore Puente Nagore Puente Pedro Grandes Pedro Grandes Pablo E. Castillo Pablo E. Castillo |
author_facet | Stefano Lutzu Karina Alviña Nagore Puente Nagore Puente Pedro Grandes Pedro Grandes Pablo E. Castillo Pablo E. Castillo |
author_sort | Stefano Lutzu |
collection | DOAJ |
description | Long-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using physiologically relevant patterns of presynaptic and postsynaptic burst activities, whole-cell patch clamp recordings, 2-photon laser calcium imaging in acute rat hippocampal slices and immunoelectron microscopy, we tested whether distinct calcium dynamics and group I metabotropic glutamate receptor (I-mGluR) subtypes control the sign of NMDAR plasticity. We found that postsynaptic calcium transients (CaTs) in response to hippocampal MF stimulation were significantly larger during the induction of NMDAR-LTP compared to NMDAR-LTD at the MF-to-CA3 pyramidal cell (MF-CA3) synapse. This difference was abolished by pharmacological blockade of mGluR5 and was significantly reduced by depletion of intracellular calcium stores, whereas blocking mGluR1 had no effect on these CaTs. In addition, we discovered that MF to hilar mossy cell (MF-MC) synapses, which share several structural and functional commonalities with MF-CA3 synapses, also undergoes NMDAR plasticity. To our surprise, however, we found that the postsynaptic distribution of I-mGluR subtypes at these two synapses differ, and the same induction protocol that induces NMDAR-LTD at MF-CA3 synapses, only triggered NMDAR-LTP at MF-MC synapses, despite a comparable calcium dynamics. Thus, postsynaptic calcium dynamics alone cannot predict the sign of NMDAR plasticity, indicating that both postsynaptic calcium rise and the relative contribution of I-mGluR subtypes likely determine the learning rules of NMDAR plasticity. |
first_indexed | 2024-04-09T19:29:29Z |
format | Article |
id | doaj.art-04facc65415b48b4b0941749226220ca |
institution | Directory Open Access Journal |
issn | 1662-5102 |
language | English |
last_indexed | 2024-04-09T19:29:29Z |
publishDate | 2023-04-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cellular Neuroscience |
spelling | doaj.art-04facc65415b48b4b0941749226220ca2023-04-05T04:36:00ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-04-011710.3389/fncel.2023.10684721068472Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampusStefano Lutzu0Karina Alviña1Nagore Puente2Nagore Puente3Pedro Grandes4Pedro Grandes5Pablo E. Castillo6Pablo E. Castillo7Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, SpainAchucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country UPV/EHU, Leioa, SpainDepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, SpainAchucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country UPV/EHU, Leioa, SpainDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, United StatesLong-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using physiologically relevant patterns of presynaptic and postsynaptic burst activities, whole-cell patch clamp recordings, 2-photon laser calcium imaging in acute rat hippocampal slices and immunoelectron microscopy, we tested whether distinct calcium dynamics and group I metabotropic glutamate receptor (I-mGluR) subtypes control the sign of NMDAR plasticity. We found that postsynaptic calcium transients (CaTs) in response to hippocampal MF stimulation were significantly larger during the induction of NMDAR-LTP compared to NMDAR-LTD at the MF-to-CA3 pyramidal cell (MF-CA3) synapse. This difference was abolished by pharmacological blockade of mGluR5 and was significantly reduced by depletion of intracellular calcium stores, whereas blocking mGluR1 had no effect on these CaTs. In addition, we discovered that MF to hilar mossy cell (MF-MC) synapses, which share several structural and functional commonalities with MF-CA3 synapses, also undergoes NMDAR plasticity. To our surprise, however, we found that the postsynaptic distribution of I-mGluR subtypes at these two synapses differ, and the same induction protocol that induces NMDAR-LTD at MF-CA3 synapses, only triggered NMDAR-LTP at MF-MC synapses, despite a comparable calcium dynamics. Thus, postsynaptic calcium dynamics alone cannot predict the sign of NMDAR plasticity, indicating that both postsynaptic calcium rise and the relative contribution of I-mGluR subtypes likely determine the learning rules of NMDAR plasticity.https://www.frontiersin.org/articles/10.3389/fncel.2023.1068472/fullCA3dentate gyrusmossy cellsynaptic plasticitycalcium signaltwo-photon laser scanning microscopy |
spellingShingle | Stefano Lutzu Karina Alviña Nagore Puente Nagore Puente Pedro Grandes Pedro Grandes Pablo E. Castillo Pablo E. Castillo Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus Frontiers in Cellular Neuroscience CA3 dentate gyrus mossy cell synaptic plasticity calcium signal two-photon laser scanning microscopy |
title | Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus |
title_full | Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus |
title_fullStr | Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus |
title_full_unstemmed | Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus |
title_short | Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus |
title_sort | target cell specific plasticity rules of nmda receptor mediated synaptic transmission in the hippocampus |
topic | CA3 dentate gyrus mossy cell synaptic plasticity calcium signal two-photon laser scanning microscopy |
url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1068472/full |
work_keys_str_mv | AT stefanolutzu targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT karinaalvina targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT nagorepuente targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT nagorepuente targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT pedrograndes targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT pedrograndes targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT pabloecastillo targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus AT pabloecastillo targetcellspecificplasticityrulesofnmdareceptormediatedsynaptictransmissioninthehippocampus |