Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices
Ascorbic acid (AA; a.k.a. vitamin C) is well known for its cellular protection in environments of high oxidative stress. Even though physiological concentrations of AA in the brain are significant (0.2–10 mM), surprisingly little is known concerning the role of AA in synaptic neurotransmission under...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/3/613 |
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| author | Segewkal H. Heruye Ted J. Warren Joseph A. Kostansek IV Samantha B. Draves Stephanie A. Matthews Peter J. West Kristina A. Simeone Timothy A. Simeone |
| author_facet | Segewkal H. Heruye Ted J. Warren Joseph A. Kostansek IV Samantha B. Draves Stephanie A. Matthews Peter J. West Kristina A. Simeone Timothy A. Simeone |
| author_sort | Segewkal H. Heruye |
| collection | DOAJ |
| description | Ascorbic acid (AA; a.k.a. vitamin C) is well known for its cellular protection in environments of high oxidative stress. Even though physiological concentrations of AA in the brain are significant (0.2–10 mM), surprisingly little is known concerning the role of AA in synaptic neurotransmission under normal, non-disease state conditions. Here, we examined AA effects on neurotransmission, plasticity and spontaneous network activity (i.e., sharp waves and high frequency oscillations; SPW-HFOs), at the synapse between area 3 and 1 of the hippocampal cornu ammonis region (CA3 and CA1) using an extracellular multi-electrode array in in vitro mouse hippocampal slices. We found that AA decreased evoked field potentials (fEPSPs, IC<sub>50</sub> = 0.64 mM) without affecting V<sub>50</sub>s or paired pulse facilitation indicating normal neurotransmitter release mechanisms. AA decreased presynaptic fiber volleys but did not change fiber volley-to-fEPSP coupling, suggesting reduced fEPSPs resulted from decreased fiber volleys. Inhibitory effects were also observed in CA1 stratum pyramidale where greater fEPSPs were required for population spikes in the presence of AA suggesting an impact on the intrinsic excitability of neurons. Other forms of synaptic plasticity and correlates of memory (i.e., short- and long-term potentiation) were also significantly reduced by AA as was the incidence of spontaneous SPW-HFOs. AA decreased SPW amplitude with a similar IC<sub>50</sub> as fEPSPs (0.65 mM). Overall, these results indicate that under normal conditions AA significantly regulates neurotransmission, plasticity, and network activity by limiting excitability. Thus, AA may participate in refinement of signal processing and memory formation, as well as protecting against pathologic excitability. |
| first_indexed | 2024-03-09T23:21:50Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T23:21:50Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-e8d2e842167c44618873d46319685bb42023-11-23T17:26:41ZengMDPI AGNutrients2072-66432022-01-0114361310.3390/nu14030613Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro SlicesSegewkal H. Heruye0Ted J. Warren1Joseph A. Kostansek IV2Samantha B. Draves3Stephanie A. Matthews4Peter J. West5Kristina A. Simeone6Timothy A. Simeone7Department of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USADepartment of Pharmacology & Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USADepartment of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, School of Medicine, Creighton University, Omaha, NE 68174, USAAscorbic acid (AA; a.k.a. vitamin C) is well known for its cellular protection in environments of high oxidative stress. Even though physiological concentrations of AA in the brain are significant (0.2–10 mM), surprisingly little is known concerning the role of AA in synaptic neurotransmission under normal, non-disease state conditions. Here, we examined AA effects on neurotransmission, plasticity and spontaneous network activity (i.e., sharp waves and high frequency oscillations; SPW-HFOs), at the synapse between area 3 and 1 of the hippocampal cornu ammonis region (CA3 and CA1) using an extracellular multi-electrode array in in vitro mouse hippocampal slices. We found that AA decreased evoked field potentials (fEPSPs, IC<sub>50</sub> = 0.64 mM) without affecting V<sub>50</sub>s or paired pulse facilitation indicating normal neurotransmitter release mechanisms. AA decreased presynaptic fiber volleys but did not change fiber volley-to-fEPSP coupling, suggesting reduced fEPSPs resulted from decreased fiber volleys. Inhibitory effects were also observed in CA1 stratum pyramidale where greater fEPSPs were required for population spikes in the presence of AA suggesting an impact on the intrinsic excitability of neurons. Other forms of synaptic plasticity and correlates of memory (i.e., short- and long-term potentiation) were also significantly reduced by AA as was the incidence of spontaneous SPW-HFOs. AA decreased SPW amplitude with a similar IC<sub>50</sub> as fEPSPs (0.65 mM). Overall, these results indicate that under normal conditions AA significantly regulates neurotransmission, plasticity, and network activity by limiting excitability. Thus, AA may participate in refinement of signal processing and memory formation, as well as protecting against pathologic excitability.https://www.mdpi.com/2072-6643/14/3/613high frequency oscillationfEPSPfiber volleysharp wavepopulation spikeE-S coupling |
| spellingShingle | Segewkal H. Heruye Ted J. Warren Joseph A. Kostansek IV Samantha B. Draves Stephanie A. Matthews Peter J. West Kristina A. Simeone Timothy A. Simeone Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices Nutrients high frequency oscillation fEPSP fiber volley sharp wave population spike E-S coupling |
| title | Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices |
| title_full | Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices |
| title_fullStr | Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices |
| title_full_unstemmed | Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices |
| title_short | Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices |
| title_sort | ascorbic acid reduces neurotransmission synaptic plasticity and spontaneous hippocampal rhythms in in vitro slices |
| topic | high frequency oscillation fEPSP fiber volley sharp wave population spike E-S coupling |
| url | https://www.mdpi.com/2072-6643/14/3/613 |
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