Late onset deficits in synaptic plasticity in the valproic acid rat model of autism
Valproic acid (VPA) is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes ne...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-01-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00023/full |
| _version_ | 1828192799636324352 |
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| author | Henry Giles Stratten Martin Henry Giles Stratten Martin Henry Giles Stratten Martin Olivier eManzoni Olivier eManzoni Olivier eManzoni |
| author_facet | Henry Giles Stratten Martin Henry Giles Stratten Martin Henry Giles Stratten Martin Olivier eManzoni Olivier eManzoni Olivier eManzoni |
| author_sort | Henry Giles Stratten Martin |
| collection | DOAJ |
| description | Valproic acid (VPA) is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC) physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP) due to an up-regulation of NMDA receptor (NMDAR) expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDA receptors during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general. |
| first_indexed | 2024-04-12T08:58:30Z |
| format | Article |
| id | doaj.art-8e09b24df2c448b88212513435935ae3 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T08:58:30Z |
| publishDate | 2014-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-8e09b24df2c448b88212513435935ae32022-12-22T03:39:18ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-01-01810.3389/fncel.2014.0002379476Late onset deficits in synaptic plasticity in the valproic acid rat model of autismHenry Giles Stratten Martin0Henry Giles Stratten Martin1Henry Giles Stratten Martin2Olivier eManzoni3Olivier eManzoni4Olivier eManzoni5INSERM U901Institut de neurobiologie de la méditerranée (INMED)Université de Aix-MarseilleINSERM U901Institut de neurobiologie de la méditerranée (INMED)Université de Aix-MarseilleValproic acid (VPA) is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC) physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP) due to an up-regulation of NMDA receptor (NMDAR) expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDA receptors during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00023/fullPrefrontal CortexValproic Acidautismsynaptic plasticityageNMDA receptor |
| spellingShingle | Henry Giles Stratten Martin Henry Giles Stratten Martin Henry Giles Stratten Martin Olivier eManzoni Olivier eManzoni Olivier eManzoni Late onset deficits in synaptic plasticity in the valproic acid rat model of autism Frontiers in Cellular Neuroscience Prefrontal Cortex Valproic Acid autism synaptic plasticity age NMDA receptor |
| title | Late onset deficits in synaptic plasticity in the valproic acid rat model of autism |
| title_full | Late onset deficits in synaptic plasticity in the valproic acid rat model of autism |
| title_fullStr | Late onset deficits in synaptic plasticity in the valproic acid rat model of autism |
| title_full_unstemmed | Late onset deficits in synaptic plasticity in the valproic acid rat model of autism |
| title_short | Late onset deficits in synaptic plasticity in the valproic acid rat model of autism |
| title_sort | late onset deficits in synaptic plasticity in the valproic acid rat model of autism |
| topic | Prefrontal Cortex Valproic Acid autism synaptic plasticity age NMDA receptor |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00023/full |
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