Insulin regulates GABAA receptor-mediated tonic currents in the prefrontal cortex
Por:
Trujeque-Ramos, Sarai, Castillo-Rolon, Diego, Galarraga, Elvira, Tapia, Dagoberto, Arenas-Lopez, Gabina, Mihailescu, Stefan, Hernandez-Lopez, Salvador
Publicada:
31 may 2018
Categoría:
Neuroscience (miscellaneous)
Resumen:
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 a-5 and d 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. © 2018 Trujeque-Ramos, Castillo-Rolón, Galarraga, Tapia, Arenas-López, Mihailescu and Hernández-López.
Filiaciones:
Trujeque-Ramos, Sarai:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City, DF, Mexico
Castillo-Rolon, Diego:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City, DF, Mexico
Galarraga, Elvira:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Mexico City, DF, Mexico
Tapia, Dagoberto:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Mexico City, DF, Mexico
Arenas-Lopez, Gabina:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City, DF, Mexico
Mihailescu, Stefan:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City, DF, Mexico
Hernandez-Lopez, Salvador:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City, DF, Mexico
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