Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices
Higher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in th...
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MDPI AG
2021-06-01
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| Online Access: | https://www.mdpi.com/2076-3425/11/6/787 |
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| author | Timothy A. Simeone Segewkal H. Heruye Joseph A. Kostansek Mary Y. Yeh Stephanie A. Matthews Kaeli K. Samson Kristina A. Simeone |
| author_facet | Timothy A. Simeone Segewkal H. Heruye Joseph A. Kostansek Mary Y. Yeh Stephanie A. Matthews Kaeli K. Samson Kristina A. Simeone |
| author_sort | Timothy A. Simeone |
| collection | DOAJ |
| description | Higher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in the CA3 region and are regulated by multiple synaptic inputs. Here, we used a multi-electrode array to determine the effects of CBZ on SPW-Rs and synaptic transmission at multiple hippocampal synapses. Our results demonstrate that CBZ reduced SPW-Rs at therapeutically relevant concentrations (IC<sub>50</sub> = 37 μM) and altered the core characteristics of ripples, important for information processing and consolidation. Moreover, CBZ inhibited neurotransmission in a synapse-specific manner. CBZ inhibition was most potent at the medial-perforant-path-to-CA3 and mossy-fiber-to-CA3 synapses (IC<sub>50</sub>s ~ 30 and 60 μM, respectively) and least potent at medial-perforant-path-to-dentate granule cell synapses (IC<sub>50</sub> ~ 120 μM). These results suggest that the synapse-specific CBZ inhibition of neurotransmission reduces SPW-Rs and that the CBZ inhibition of SPW-Rs may underlie the cognitive impairments observed with therapeutic doses of CBZ. |
| first_indexed | 2024-03-10T10:24:43Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T10:24:43Z |
| publishDate | 2021-06-01 |
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| spelling | doaj.art-b56020e7b7784c7ea5d9445a42f94dc52023-11-22T00:06:37ZengMDPI AGBrain Sciences2076-34252021-06-0111678710.3390/brainsci11060787Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal SlicesTimothy A. Simeone0Segewkal H. Heruye1Joseph A. Kostansek2Mary Y. Yeh3Stephanie A. Matthews4Kaeli K. Samson5Kristina A. Simeone6Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USADepartment of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68174, USAHigher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in the CA3 region and are regulated by multiple synaptic inputs. Here, we used a multi-electrode array to determine the effects of CBZ on SPW-Rs and synaptic transmission at multiple hippocampal synapses. Our results demonstrate that CBZ reduced SPW-Rs at therapeutically relevant concentrations (IC<sub>50</sub> = 37 μM) and altered the core characteristics of ripples, important for information processing and consolidation. Moreover, CBZ inhibited neurotransmission in a synapse-specific manner. CBZ inhibition was most potent at the medial-perforant-path-to-CA3 and mossy-fiber-to-CA3 synapses (IC<sub>50</sub>s ~ 30 and 60 μM, respectively) and least potent at medial-perforant-path-to-dentate granule cell synapses (IC<sub>50</sub> ~ 120 μM). These results suggest that the synapse-specific CBZ inhibition of neurotransmission reduces SPW-Rs and that the CBZ inhibition of SPW-Rs may underlie the cognitive impairments observed with therapeutic doses of CBZ.https://www.mdpi.com/2076-3425/11/6/787cognitive impairmentepilepsyadverse effecthigh frequency oscillations |
| spellingShingle | Timothy A. Simeone Segewkal H. Heruye Joseph A. Kostansek Mary Y. Yeh Stephanie A. Matthews Kaeli K. Samson Kristina A. Simeone Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices Brain Sciences cognitive impairment epilepsy adverse effect high frequency oscillations |
| title | Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices |
| title_full | Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices |
| title_fullStr | Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices |
| title_full_unstemmed | Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices |
| title_short | Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices |
| title_sort | carbamazepine reduces sharp wave ripple complexes and exerts synapse specific inhibition of neurotransmission in ex vivo hippocampal slices |
| topic | cognitive impairment epilepsy adverse effect high frequency oscillations |
| url | https://www.mdpi.com/2076-3425/11/6/787 |
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