Mature BDNF, but not proBDNF, reduces excitability of fast-spiking interneurons in mouse dentate gyrus.
Mature BDNF and its precursor proBDNF may both be secreted to exert opposite effects on synaptic plasticity in the hippocampus. However, it is unknown how proBDNF and mature BDNF affect the excitability of GABAergic interneurons and thereby regulate GABAergic inhibition. We made recordings of GABAergic spontaneous IPSCs (sIPSCs) in mouse dentate gyrus granule cells and found that chronic or acute BDNF reductions led to large increases in the sIPSC frequencies, which were TTX (tetrodotoxin) sensitive and therefore action-potential driven. Conversely, addition of mature BDNF, but not proBDNF, within minutes led to a decrease in the sIPSC frequency to 44%. Direct recordings from fast-spiking GABAergic interneurons revealed that mature BDNF reduced their excitability and depressed their action potential firing, whereas proBDNF had no effect. Using the TrkB inhibitor K-252a, or mice deficient for the common neurotrophin receptor p75(NTR), the regulation of GABAergic activity was shown specifically to be mediated by BDNF binding to the neurotrophin receptor TrkB. In agreement, immunohistochemistry demonstrated that TrkB, but not p75(NTR), was expressed in parvalbumin-positive interneurons. Our results suggest that mature BDNF decreases the excitability of GABAergic interneurons via activation of TrkB, while proBDNF does not impact on GABAergic activity. Thus, by affecting the firing of GABAergic interneurons, mature BDNF may play an important role in regulating network oscillations in the hippocampus.
Holm
Mai Marie
MM
Department of Physiology and Biophysics, Aarhus University, DK-8000 Aarhus, Denmark.
Nieto-Gonzalez
Jose Luis
JL
Vardya
Irina
I
Vaegter
Christian Bjerggaard
CB
Nykjaer
Anders
A
Jensen
Kimmo
K
D000200:Action Potentials; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D020813:Receptor, trkB / Q000378:metabolism; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB