BDNF Depresses Excitability of Parvalbumin-Positive Interneurons through an M-Like Current in Rat Dentate GyrusReportar como inadecuado




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In addition to their classical roles in neuronal growth, survival and differentiation, neurotrophins are also rapid regulators of excitability, synaptic transmission and activity-dependent synaptic plasticity. We have recently shown that mature BDNF Brain Derived Neurotrophic Factor, but not proBDNF, modulates the excitability of interneurons in dentate gyrus within minutes. Here, we used brain slice patch-clamp recordings to study the mechanisms through which BDNF modulates the firing of interneurons in rat dentate gyrus by binding to TrkB receptors. Bath application of BDNF 15 ng-ml under current-clamp decreased the firing frequency by 80% and input resistance, blocking the delayed firing observed at near-threshold voltage ranges, with no changes in resting membrane potential or action potential waveform. Using TEA tetraethylammonium, or XE991a Kv7-KCNQ channel antagonist, the effect of BDNF was abolished, whereas application of retigabine a Kv7-KCNQ channel opener mimicked the effect of BDNF, suggesting that the M-current could be implicated in the modulation of the firing. In voltage-clamp experiments, BDNF increased the M-like current amplitude with no change in holding current. This effect was again blocked by XE991 and mimicked by retigabine, the latter accompanied with a change in holding current. In agreement with the electrophysiology, parvalbumin-positive interneurons co-expressed TrkB receptors and Kv7.2-KCNQ2 channels. In conclusion, BDNF depresses the excitability of interneurons by activating an M-like current and possibly blocking Kv1 channels, thereby controlling interneuron resting membrane potential and excitability.



Autor: Jose Luis Nieto-Gonzalez , Kimmo Jensen

Fuente: http://plos.srce.hr/



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