Endogenous BDNF regulates tonic inhibition.
Field:	Neurotransmitters and receptors
Authors:	Olofsdotter, Klara Lindvall, Olle Asztély, Fredrik
Address of presenting author:	Restorative Neurology WNC, Sölvegatan 17 S-221 85 Lund Sweden
E-mail:	klara.olofsdotter@neurol.lu.se
Phone:	+46 46 222 05 50
Fax:	+46 46 222 05 60
Text of abstract:	ABSTRACT The aim of this study was to explore the role of endogenous neurotrophins for inhibitory synaptic transmission in the dentate gyrus of adult mice. To study the effects of lowered levels of endogenous BDNF and NT-3 we used heterozygous knockout mice or Trk-IgG scavenging proteins. Patch-clamp recordings from dentate granule cells in brain slices showed that the frequency of miniature inhibitory postsynaptic currents was higher in BDNF +/- mice than in their +/+ littermates, while kinetics and amplitude of these inhibitory currents was unchanged. Similar results were obtained in brain slices from BDNF +/+ mice incubated with TrkB-IgG, which scavenges endogenous BDNF. The increased inhibitory synaptic activity in BDNF +/- mice was accompanied with decreased excitability of the granule cells. No differences in the frequency, amplitude or kinetics of miniature inhibitory postsynaptic currents were seen between NT-3 +/- and +/+ mice. These results suggest that endogenous BDNF, but not NT-3, has acute modulatory effects on tonic inhibition onto dentate granule cells. Our data suggest that this effect is presynaptic, which means that BDNF acts on the inhibitory interneurones which in turn affect the excitability of dentate granule cells. We propose that through this mechanism BDNF can change the gating/filtering properties of the dentate gyrus for incoming information from the entorhinal cortex to hippocampus. This will have consequences for the recruitment of hippocampal neural circuitries both under physiological and pathological conditions, such as epileptogenesis.
Keywords:	BDNF, dentate gyrus, GABA, inhibition, NT-3

Created 2000-03-15