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Investigating the Behavioral and Electrophysiological Changes in Neuronal Excitability and Voltage-gated Ih channel Current in a Rat Model of Autism Induced by Prenatal Exposure to Valproic Acid in the Offspring.
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Razieh Hajisoltani   , Seyed Asaad Karimi , Mona Rahdar , Narges Hosseinmardi , Gila Behzadi , Mahyar Janahmadi |
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Abstract: (256 Views) |
Introduction: Autism spectrum disorder (ASD) is a common neuropsychiatric disorder, which is characterized by impairment in social interaction and cognitive behaviors. However, there is not much electrophysiological data available on alterations of neuronal excitability in autism. Here, we assessed the pattern of neuronal excitability and the possible contribution of Ih current to the altered excitability of hippocampal CA1 pyramidal neurons in a rat model of VPA-induced ASD-like behavior.
Methods and Materials: Pregnant Wistar rats received Valproic Acid (VPA, 500mg/kg) at gestational day 12.5. All offspring were subjected to behavioral tests to verify the induction of ASD-like behaviors. On postnatal day (PND) 45, whole-cell patch-clamp recordings were performed on hippocampal CA1 pyramidal neurons in slices obtained from control and prenatal VPA-exposed pups, under current and voltage-clamp conditions.
Results: Our results showed that beside the induction of behavioral abnormalities in ASD pups, higher excitability of hippocampal CA1 pyramidal neurons was also prominent, as evidenced by a significant increase in the spontaneous firing frequency and evoked firing rate, as well as a significant decrease in the rheobase current. In the VPA-exposed group, the steady-state (ISS) Ih current amplitude was significantly smaller than control cells. The Ih half-activation voltage shifted toward more negative potentials in the VPA-exposed group. The sag ratio was also significantly less than the control cells. Moreover, the cell soma size was shifted toward smaller diameter in VPA-exposed group.
Conclusion: Overall, induction of ASD-like behaviors was associated with neuronal hyperexcitability, which, at least in part, could be attributed to the changes in Ih channels function.
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| Keywords: Valproic Acid, Autism Spectrum Disorder, Ih channel current, CA1 pyramidal neurons, Whole-Cell Patch-Clamp |
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Full-Text [PDF 261 kb]
(33 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/11 | Accepted: 2023/08/23 | Published: 2023/08/23
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