title: BDNF Depresses Excitability of Parvalbumin-Positive Interneurons through an M-Like Current in Rat Dentate Gyrus.
abstract: 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 XE991(a 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.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Nieto-Gonzalez
authors.forename: Kimmo
authors.initials: K
authors.lastname: Jensen
mesh_terms: D000200:Action Potentials; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010320:Parvalbumins; D026902:Potassium Channel Blockers; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins