Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome
The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compare...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2018/9235796 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832559519393120256 |
|---|---|
| author | Jonah J. Scott-McKean Adriano L. Roque Krystyna Surewicz Mark W. Johnson Witold K. Surewicz Alberto C. S. Costa |
| author_facet | Jonah J. Scott-McKean Adriano L. Roque Krystyna Surewicz Mark W. Johnson Witold K. Surewicz Alberto C. S. Costa |
| author_sort | Jonah J. Scott-McKean |
| collection | DOAJ |
| description | The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 μM memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 μM picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices. |
| format | Article |
| id | doaj-art-de446ed5df69408d9456fc5ed15c7656 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-de446ed5df69408d9456fc5ed15c76562025-02-03T01:29:54ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/92357969235796Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down SyndromeJonah J. Scott-McKean0Adriano L. Roque1Krystyna Surewicz2Mark W. Johnson3Witold K. Surewicz4Alberto C. S. Costa5Division of Pediatric Neurology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USADivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USADivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USAThe Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 μM memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 μM picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices.http://dx.doi.org/10.1155/2018/9235796 |
| spellingShingle | Jonah J. Scott-McKean Adriano L. Roque Krystyna Surewicz Mark W. Johnson Witold K. Surewicz Alberto C. S. Costa Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome Neural Plasticity |
| title | Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome |
| title_full | Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome |
| title_fullStr | Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome |
| title_full_unstemmed | Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome |
| title_short | Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome |
| title_sort | pharmacological modulation of three modalities of ca1 hippocampal long term potentiation in the ts65dn mouse model of down syndrome |
| url | http://dx.doi.org/10.1155/2018/9235796 |
| work_keys_str_mv | AT jonahjscottmckean pharmacologicalmodulationofthreemodalitiesofca1hippocampallongtermpotentiationinthets65dnmousemodelofdownsyndrome AT adrianolroque pharmacologicalmodulationofthreemodalitiesofca1hippocampallongtermpotentiationinthets65dnmousemodelofdownsyndrome AT krystynasurewicz pharmacologicalmodulationofthreemodalitiesofca1hippocampallongtermpotentiationinthets65dnmousemodelofdownsyndrome AT markwjohnson pharmacologicalmodulationofthreemodalitiesofca1hippocampallongtermpotentiationinthets65dnmousemodelofdownsyndrome AT witoldksurewicz pharmacologicalmodulationofthreemodalitiesofca1hippocampallongtermpotentiationinthets65dnmousemodelofdownsyndrome AT albertocscosta pharmacologicalmodulationofthreemodalitiesofca1hippocampallongtermpotentiationinthets65dnmousemodelofdownsyndrome |