Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex
Recent studies, have shown that insulin increases extrasynaptic GABAA receptor-mediated currents in the hippocampus, causing alterations of neuronal excitability. The prefrontal cortex (PFC) is another brain area which is involved in cognition functions and expresses insulin receptors. Here, we used...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00345/full |
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| author | Saraí Trujeque-Ramos Diego Castillo-Rolón Elvira Galarraga Dagoberto Tapia Gabina Arenas-López Stefan Mihailescu Salvador Hernández-López |
| author_facet | Saraí Trujeque-Ramos Diego Castillo-Rolón Elvira Galarraga Dagoberto Tapia Gabina Arenas-López Stefan Mihailescu Salvador Hernández-López |
| author_sort | Saraí Trujeque-Ramos |
| collection | DOAJ |
| description | Recent studies, have shown that insulin increases extrasynaptic GABAA receptor-mediated currents in the hippocampus, causing alterations of neuronal excitability. The prefrontal cortex (PFC) is another brain area which is involved in cognition functions and expresses insulin receptors. Here, we used electrophysiological, molecular, and immunocytochemical techniques to examine the effect of insulin on the extrasynaptic GABAA receptor-mediated tonic currents in brain slices. We found that insulin (20–500 nM) increases GABAA-mediated tonic currents. Our results suggest that insulin promotes the trafficking of extrasynaptic GABAA receptors from the cytoplasm to the cell membrane. Western blot analysis and immunocytochemistry showed that PFC extrasynaptic GABAA receptors contain α-5 and δ subunits. Insulin effect on tonic currents decreased the firing rate and neuronal excitability in layer 5–6 PFC cells. These effects of insulin were dependent on the activation of the PI3K enzyme, a key mediator of the insulin response within the brain. Taken together, these results suggest that insulin modulation of the GABAA-mediated tonic currents can modify the activity of neural circuits within the PFC. These actions could help to explain the alterations of cognitive processes associated with changes in insulin signaling. |
| first_indexed | 2024-12-14T21:02:00Z |
| format | Article |
| id | doaj.art-5454d4c0ca224d1db8f96fa3f2cc1f0e |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-14T21:02:00Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-5454d4c0ca224d1db8f96fa3f2cc1f0e2022-12-21T22:47:33ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-05-011210.3389/fnins.2018.00345372396Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal CortexSaraí Trujeque-Ramos0Diego Castillo-Rolón1Elvira Galarraga2Dagoberto Tapia3Gabina Arenas-López4Stefan Mihailescu5Salvador Hernández-López6Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoDivisión de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoDivisión de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, MexicoRecent studies, have shown that insulin increases extrasynaptic GABAA receptor-mediated currents in the hippocampus, causing alterations of neuronal excitability. The prefrontal cortex (PFC) is another brain area which is involved in cognition functions and expresses insulin receptors. Here, we used electrophysiological, molecular, and immunocytochemical techniques to examine the effect of insulin on the extrasynaptic GABAA receptor-mediated tonic currents in brain slices. We found that insulin (20–500 nM) increases GABAA-mediated tonic currents. Our results suggest that insulin promotes the trafficking of extrasynaptic GABAA receptors from the cytoplasm to the cell membrane. Western blot analysis and immunocytochemistry showed that PFC extrasynaptic GABAA receptors contain α-5 and δ subunits. Insulin effect on tonic currents decreased the firing rate and neuronal excitability in layer 5–6 PFC cells. These effects of insulin were dependent on the activation of the PI3K enzyme, a key mediator of the insulin response within the brain. Taken together, these results suggest that insulin modulation of the GABAA-mediated tonic currents can modify the activity of neural circuits within the PFC. These actions could help to explain the alterations of cognitive processes associated with changes in insulin signaling.https://www.frontiersin.org/article/10.3389/fnins.2018.00345/fullextrasynaptic GABAA receptorsambient GABAreceptor traffickingbrain slicesneuronal excitability |
| spellingShingle | Saraí Trujeque-Ramos Diego Castillo-Rolón Elvira Galarraga Dagoberto Tapia Gabina Arenas-López Stefan Mihailescu Salvador Hernández-López Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex Frontiers in Neuroscience extrasynaptic GABAA receptors ambient GABA receptor trafficking brain slices neuronal excitability |
| title | Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex |
| title_full | Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex |
| title_fullStr | Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex |
| title_full_unstemmed | Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex |
| title_short | Insulin Regulates GABAA Receptor-Mediated Tonic Currents in the Prefrontal Cortex |
| title_sort | insulin regulates gabaa receptor mediated tonic currents in the prefrontal cortex |
| topic | extrasynaptic GABAA receptors ambient GABA receptor trafficking brain slices neuronal excitability |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00345/full |
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