Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction
The induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission entails pre- and postsynaptic Ca2+ signals, which represent transient increments in cytoplasmic free Ca2+ concentration. In diverse synapse types, Ca2+ release from intracellular stores contrib...
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00403/full |
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| author | Alejandra Arias-Cavieres Genaro C. Barrientos Gina Sánchez Gina Sánchez Claudio Elgueta Pablo Muñoz Cecilia Hidalgo Cecilia Hidalgo Cecilia Hidalgo |
| author_facet | Alejandra Arias-Cavieres Genaro C. Barrientos Gina Sánchez Gina Sánchez Claudio Elgueta Pablo Muñoz Cecilia Hidalgo Cecilia Hidalgo Cecilia Hidalgo |
| author_sort | Alejandra Arias-Cavieres |
| collection | DOAJ |
| description | The induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission entails pre- and postsynaptic Ca2+ signals, which represent transient increments in cytoplasmic free Ca2+ concentration. In diverse synapse types, Ca2+ release from intracellular stores contributes to amplify the Ca2+ signals initially generated by activation of neuronal Ca2+ entry pathways. Here, we used hippocampal slices from young male rats to evaluate whether pharmacological activation or inhibition of Ca2+ release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels modifies LTD induction at Schaffer collateral-CA1 synapses. Pre-incubation of slices with ryanodine (1 μM, 1 h) or caffeine (1 mM, 30 min) to promote RyR-mediated Ca2+ release facilitated LTD induction by low frequency stimulation (LFS), but did not affect the amplitude of synaptic transmission, the profiles of field excitatory postsynaptic potentials (fEPSP) or the paired-pulse (PP) responses. Conversely, treatment with inhibitory ryanodine (20 μM, 1 h) to suppress RyR-mediated Ca2+ release prevented LTD induction, but did not affect baseline synaptic transmission or PP responses. Previous literature reports indicate that LTD induction requires presynaptic CaMKII activity. We found that 1 h after applying the LTD induction protocol, slices displayed a significant increase in CaMKII phosphorylation relative to the levels exhibited by un-stimulated (naïve) slices. In addition, LTD induction (1 h) enhanced the phosphorylation of the presynaptic protein Synapsin I at a CaMKII-dependent phosphorylation site, indicating that LTD induction stimulates presynaptic CaMKII activity. Pre-incubation of slices with 20 μM ryanodine abolished the increased CaMKII and Synapsin I phosphorylation induced by LTD, whereas naïve slices pre-incubated with inhibitory ryanodine displayed similar CaMKII and Synapsin I phosphorylation levels as naïve control slices. We posit that inhibitory ryanodine suppressed LTD-induced presynaptic CaMKII activity, as evidenced by the suppression of Synapsin I phosphorylation induced by LTD. Accordingly, we propose that presynaptic RyR-mediated Ca2+ signals contribute to LTD induction at Schaffer collateral-CA1 synapses. |
| first_indexed | 2024-12-12T21:54:34Z |
| format | Article |
| id | doaj.art-6af380ccd94e4159a5ceccd18e591888 |
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| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-12T21:54:34Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-6af380ccd94e4159a5ceccd18e5918882022-12-22T00:10:41ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-11-011210.3389/fncel.2018.00403332388Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD InductionAlejandra Arias-Cavieres0Genaro C. Barrientos1Gina Sánchez2Gina Sánchez3Claudio Elgueta4Pablo Muñoz5Cecilia Hidalgo6Cecilia Hidalgo7Cecilia Hidalgo8Biomedical Neuroscience Institute (BNI), Faculty of Medicine, Universidad de Chile, Santiago, ChilePhysiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileBiomedical Neuroscience Institute (BNI), Faculty of Medicine, Universidad de Chile, Santiago, ChilePathophysiology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileSystemic and Cellular Neurophysiology, Physiology Institute I, Medical Faculty, University of Freiburg, Freiburg, GermanyPathology and Physiology Department, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso, ChileBiomedical Neuroscience Institute (BNI), Faculty of Medicine, Universidad de Chile, Santiago, ChilePhysiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileDepartment of Neuroscience and Center of Molecular Studies of the Cell, Faculty of Medicine, Universidad de Chile, Santiago, ChileThe induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission entails pre- and postsynaptic Ca2+ signals, which represent transient increments in cytoplasmic free Ca2+ concentration. In diverse synapse types, Ca2+ release from intracellular stores contributes to amplify the Ca2+ signals initially generated by activation of neuronal Ca2+ entry pathways. Here, we used hippocampal slices from young male rats to evaluate whether pharmacological activation or inhibition of Ca2+ release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels modifies LTD induction at Schaffer collateral-CA1 synapses. Pre-incubation of slices with ryanodine (1 μM, 1 h) or caffeine (1 mM, 30 min) to promote RyR-mediated Ca2+ release facilitated LTD induction by low frequency stimulation (LFS), but did not affect the amplitude of synaptic transmission, the profiles of field excitatory postsynaptic potentials (fEPSP) or the paired-pulse (PP) responses. Conversely, treatment with inhibitory ryanodine (20 μM, 1 h) to suppress RyR-mediated Ca2+ release prevented LTD induction, but did not affect baseline synaptic transmission or PP responses. Previous literature reports indicate that LTD induction requires presynaptic CaMKII activity. We found that 1 h after applying the LTD induction protocol, slices displayed a significant increase in CaMKII phosphorylation relative to the levels exhibited by un-stimulated (naïve) slices. In addition, LTD induction (1 h) enhanced the phosphorylation of the presynaptic protein Synapsin I at a CaMKII-dependent phosphorylation site, indicating that LTD induction stimulates presynaptic CaMKII activity. Pre-incubation of slices with 20 μM ryanodine abolished the increased CaMKII and Synapsin I phosphorylation induced by LTD, whereas naïve slices pre-incubated with inhibitory ryanodine displayed similar CaMKII and Synapsin I phosphorylation levels as naïve control slices. We posit that inhibitory ryanodine suppressed LTD-induced presynaptic CaMKII activity, as evidenced by the suppression of Synapsin I phosphorylation induced by LTD. Accordingly, we propose that presynaptic RyR-mediated Ca2+ signals contribute to LTD induction at Schaffer collateral-CA1 synapses.https://www.frontiersin.org/article/10.3389/fncel.2018.00403/fullcalcium signalsryanodinecaffeinebasal synaptic transmissionlow-frequency stimulation |
| spellingShingle | Alejandra Arias-Cavieres Genaro C. Barrientos Gina Sánchez Gina Sánchez Claudio Elgueta Pablo Muñoz Cecilia Hidalgo Cecilia Hidalgo Cecilia Hidalgo Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction Frontiers in Cellular Neuroscience calcium signals ryanodine caffeine basal synaptic transmission low-frequency stimulation |
| title | Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction |
| title_full | Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction |
| title_fullStr | Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction |
| title_full_unstemmed | Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction |
| title_short | Ryanodine Receptor-Mediated Calcium Release Has a Key Role in Hippocampal LTD Induction |
| title_sort | ryanodine receptor mediated calcium release has a key role in hippocampal ltd induction |
| topic | calcium signals ryanodine caffeine basal synaptic transmission low-frequency stimulation |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00403/full |
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