Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia
Maternal immune activation (MIA) and juvenile social isolation (SI) are two most prevalent and widely accepted environmental insults that could increase the propensity of psychiatric illnesses. Using a two-hit mouse model, we examined the impact of the combination of these two factors on animal beha...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-12-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00554/full |
| _version_ | 1819135927044276224 |
|---|---|
| author | Zhen Mi Jun Yang Quansheng He Xiaowen Zhang Yujie Xiao Yousheng Shu Yousheng Shu |
| author_facet | Zhen Mi Jun Yang Quansheng He Xiaowen Zhang Yujie Xiao Yousheng Shu Yousheng Shu |
| author_sort | Zhen Mi |
| collection | DOAJ |
| description | Maternal immune activation (MIA) and juvenile social isolation (SI) are two most prevalent and widely accepted environmental insults that could increase the propensity of psychiatric illnesses. Using a two-hit mouse model, we examined the impact of the combination of these two factors on animal behaviors, neuronal excitability and expressions of voltage-gated sodium (Nav) and small conductance calcium-activated potassium (SK) channels in the prefrontal cortex (PFC). We found that MIA-SI induced a number of schizophrenia-related behavioral deficits. Patch clamp recordings revealed alterations in electrophysiological properties of PFC layer-5 pyramidal cells, including hyperpolarized resting membrane potential (RMP), increased input resistance and enhanced medium after-hyperpolarization (mAHP). MIA-SI also increased the ratio of the maximal slope of somatodendritic potential to the peak slope of action potential upstroke, indicating a change in perisomatic Nav availability. Consistently, MIA-SI significantly increased the expression level of Nav1.2 and SK3 channels that contribute to the somatodendritic potential and the mAHP, respectively. Together, these changes may alter neuronal signaling in the PFC and behavioral states, representing a molecular imprint of environmental insults associated with neuropsychiatric illnesses. |
| first_indexed | 2024-12-22T10:26:51Z |
| format | Article |
| id | doaj.art-6fc511882afd437f8fb2982f1defbd77 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T10:26:51Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-6fc511882afd437f8fb2982f1defbd772022-12-21T18:29:28ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-12-011310.3389/fncel.2019.00554500132Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of SchizophreniaZhen Mi0Jun Yang1Quansheng He2Xiaowen Zhang3Yujie Xiao4Yousheng Shu5Yousheng Shu6State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, ChinaState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, ChinaState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, ChinaState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, ChinaState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, ChinaState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, ChinaIDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, ChinaMaternal immune activation (MIA) and juvenile social isolation (SI) are two most prevalent and widely accepted environmental insults that could increase the propensity of psychiatric illnesses. Using a two-hit mouse model, we examined the impact of the combination of these two factors on animal behaviors, neuronal excitability and expressions of voltage-gated sodium (Nav) and small conductance calcium-activated potassium (SK) channels in the prefrontal cortex (PFC). We found that MIA-SI induced a number of schizophrenia-related behavioral deficits. Patch clamp recordings revealed alterations in electrophysiological properties of PFC layer-5 pyramidal cells, including hyperpolarized resting membrane potential (RMP), increased input resistance and enhanced medium after-hyperpolarization (mAHP). MIA-SI also increased the ratio of the maximal slope of somatodendritic potential to the peak slope of action potential upstroke, indicating a change in perisomatic Nav availability. Consistently, MIA-SI significantly increased the expression level of Nav1.2 and SK3 channels that contribute to the somatodendritic potential and the mAHP, respectively. Together, these changes may alter neuronal signaling in the PFC and behavioral states, representing a molecular imprint of environmental insults associated with neuropsychiatric illnesses.https://www.frontiersin.org/article/10.3389/fncel.2019.00554/fullschizophreniaion channelneuronal excitabilityaction potentialprefrontal cortexSK channel |
| spellingShingle | Zhen Mi Jun Yang Quansheng He Xiaowen Zhang Yujie Xiao Yousheng Shu Yousheng Shu Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia Frontiers in Cellular Neuroscience schizophrenia ion channel neuronal excitability action potential prefrontal cortex SK channel |
| title | Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia |
| title_full | Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia |
| title_fullStr | Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia |
| title_full_unstemmed | Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia |
| title_short | Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia |
| title_sort | alterations of electrophysiological properties and ion channel expression in prefrontal cortex of a mouse model of schizophrenia |
| topic | schizophrenia ion channel neuronal excitability action potential prefrontal cortex SK channel |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00554/full |
| work_keys_str_mv | AT zhenmi alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia AT junyang alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia AT quanshenghe alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia AT xiaowenzhang alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia AT yujiexiao alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia AT youshengshu alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia AT youshengshu alterationsofelectrophysiologicalpropertiesandionchannelexpressioninprefrontalcortexofamousemodelofschizophrenia |