Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats
Schizophrenia (SZ) is associated with changes in the structure and function of several brain areas. Several findings suggest that these impairments are related to a dysfunction in γ-aminobutyric acid (GABA) neurotransmission in brain areas such as the medial prefrontal cortex (mPFC), the hippocampus...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00372/full |
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| author | Miguel Ángel Pérez Miguel Ángel Pérez Miguel Ángel Pérez Camila Morales Odra Santander Odra Santander Odra Santander Francisca García Francisca García Francisca García Isabel Gómez Valentín Peñaloza-Sancho Valentín Peñaloza-Sancho Pablo Fuentealba Alexies Dagnino-Subiabre Alexies Dagnino-Subiabre Pablo R. Moya Pablo R. Moya Marco Fuenzalida Marco Fuenzalida |
| author_facet | Miguel Ángel Pérez Miguel Ángel Pérez Miguel Ángel Pérez Camila Morales Odra Santander Odra Santander Odra Santander Francisca García Francisca García Francisca García Isabel Gómez Valentín Peñaloza-Sancho Valentín Peñaloza-Sancho Pablo Fuentealba Alexies Dagnino-Subiabre Alexies Dagnino-Subiabre Pablo R. Moya Pablo R. Moya Marco Fuenzalida Marco Fuenzalida |
| author_sort | Miguel Ángel Pérez |
| collection | DOAJ |
| description | Schizophrenia (SZ) is associated with changes in the structure and function of several brain areas. Several findings suggest that these impairments are related to a dysfunction in γ-aminobutyric acid (GABA) neurotransmission in brain areas such as the medial prefrontal cortex (mPFC), the hippocampus (HPC) and the primary auditory cortex (A1); however, it is still unclear how the GABAergic system is disrupted in these brain areas. Here, we examined the effect of ketamine (Ket) administration during late adolescence in rats on inhibition in the mPFC-, ventral HPC (vHPC), and A1. We observe that Ket treatment reduced the expression of the calcium-binding protein parvalbumin (PV) and the GABA-producing enzyme glutamic acid decarboxylase 67 (GAD67) as well as decreased inhibitory synaptic efficacy in the mPFC. In addition, Ket-treated rats performed worse in executive tasks that depend on the integrity and proper functioning of the mPFC. Conversely, we do not find such changes in vHPC or A1. Together, our results provide strong experimental support for the hypothesis that during adolescence, the function of the mPFC is more susceptible than that of HPC or A1 to NMDAR hypofunction, showing apparent structure specificity. Thus, the impairment of inhibitory circuitry in mPFC could be a convergent primary site of SZ-like behavior during the adulthood. |
| first_indexed | 2024-12-19T10:14:46Z |
| format | Article |
| id | doaj.art-239005d8197d42ec83e796f39b6f1259 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-19T10:14:46Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-239005d8197d42ec83e796f39b6f12592022-12-21T20:26:15ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-08-011310.3389/fncel.2019.00372470973Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult RatsMiguel Ángel Pérez0Miguel Ángel Pérez1Miguel Ángel Pérez2Camila Morales3Odra Santander4Odra Santander5Odra Santander6Francisca García7Francisca García8Francisca García9Isabel Gómez10Valentín Peñaloza-Sancho11Valentín Peñaloza-Sancho12Pablo Fuentealba13Alexies Dagnino-Subiabre14Alexies Dagnino-Subiabre15Pablo R. Moya16Pablo R. Moya17Marco Fuenzalida18Marco Fuenzalida19Laboratorio de Plasticidad Neuronal, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, ChileEscuela de Ciencias de la Salud, Carrera de Kinesiología, Universidad Viña del Mar, Viña del Mar, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileLaboratorio de Plasticidad Neuronal, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, ChilePrograma de Doctorado en Ciencias, Mención Neurociencias, Universidad de Valparaíso, ChileLaboratorio de Plasticidad Neuronal, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, ChilePrograma de Doctorado en Ciencias, Mención Neurociencias, Universidad de Valparaíso, ChileLaboratorio de Neurogenética, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, ChileLaboratorio de Neurobiología del Estrés, Universidad de Valparaíso, Valparaíso, ChileLaboratory of Neural Circuits, Centro de Neurociencia Universidad Católica, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, ChileLaboratorio de Neurobiología del Estrés, Universidad de Valparaíso, Valparaíso, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileLaboratorio de Neurogenética, Universidad de Valparaíso, Valparaíso, ChileLaboratorio de Plasticidad Neuronal, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, ChileSchizophrenia (SZ) is associated with changes in the structure and function of several brain areas. Several findings suggest that these impairments are related to a dysfunction in γ-aminobutyric acid (GABA) neurotransmission in brain areas such as the medial prefrontal cortex (mPFC), the hippocampus (HPC) and the primary auditory cortex (A1); however, it is still unclear how the GABAergic system is disrupted in these brain areas. Here, we examined the effect of ketamine (Ket) administration during late adolescence in rats on inhibition in the mPFC-, ventral HPC (vHPC), and A1. We observe that Ket treatment reduced the expression of the calcium-binding protein parvalbumin (PV) and the GABA-producing enzyme glutamic acid decarboxylase 67 (GAD67) as well as decreased inhibitory synaptic efficacy in the mPFC. In addition, Ket-treated rats performed worse in executive tasks that depend on the integrity and proper functioning of the mPFC. Conversely, we do not find such changes in vHPC or A1. Together, our results provide strong experimental support for the hypothesis that during adolescence, the function of the mPFC is more susceptible than that of HPC or A1 to NMDAR hypofunction, showing apparent structure specificity. Thus, the impairment of inhibitory circuitry in mPFC could be a convergent primary site of SZ-like behavior during the adulthood.https://www.frontiersin.org/article/10.3389/fncel.2019.00372/fullketaminelate adolescencePV-INsGABAmPFCschizophrenia-like behavior |
| spellingShingle | Miguel Ángel Pérez Miguel Ángel Pérez Miguel Ángel Pérez Camila Morales Odra Santander Odra Santander Odra Santander Francisca García Francisca García Francisca García Isabel Gómez Valentín Peñaloza-Sancho Valentín Peñaloza-Sancho Pablo Fuentealba Alexies Dagnino-Subiabre Alexies Dagnino-Subiabre Pablo R. Moya Pablo R. Moya Marco Fuenzalida Marco Fuenzalida Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats Frontiers in Cellular Neuroscience ketamine late adolescence PV-INs GABA mPFC schizophrenia-like behavior |
| title | Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats |
| title_full | Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats |
| title_fullStr | Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats |
| title_full_unstemmed | Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats |
| title_short | Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats |
| title_sort | ketamine treatment during late adolescence impairs inhibitory synaptic transmission in the prefrontal cortex and working memory in adult rats |
| topic | ketamine late adolescence PV-INs GABA mPFC schizophrenia-like behavior |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00372/full |
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