Rapid modulation of inhibitory synaptic currents in cerebellar Purkinje cells by BDNF.
The present study examined the acute effects of exogenous BDNF on inhibitory synaptic currents in Purkinje cells in cerebellar cultures. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded in cultures (20-30 days in vitro), using discontinuous single electrode voltage clamp (dSEVC) technique. The effects of BDNF were studied in untreated control cultures and in cultures in which the endogenous levels of BDNF were decreased by chronic block of neural activity with tetrodotoxin (TTX). Chronic activity deprivation did not alter the amplitude of mIPSCs in Purkinje cells, and acute application of BDNF (50 ng/ml) to Purkinje cells in TTX-treated cultures significantly potentiated the amplitude and frequency of mIPSCs. By contrast, acute application of BDNF (50 ng/ml) produced no significant changes on mIPSC activity in control neurons. At higher concentrations of BDNF (100 ng/ml), comparable effects on mIPSC activity were also observed in control neurons. Preincubation of cerebellar cultures with K252a, an inhibitor of tyrosine kinases, effectively blocked the effects of BDNF on mIPSCs. These results indicate that functional inhibitory synapses develop in the absence of neural activity, and that activation of TrkB receptors by BDNF modulates inhibitory neurotransmission in Purkinje cells at both pre- and postsynaptic sites.
Neurology Research, Veterans Affairs Medical Center, Portland, Oregon 97239, USA. drakebar@ohsu.edu
Rosemarie
R
Drake-Baumann
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism*; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D013779:Tetrodotoxin; C049985:staurosporine aglycone; D020813:Receptor, trkB