Premium
BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA A receptor surface expression
Author(s) -
Brünig Ina,
Penschuck Silke,
Berninger Benedikt,
Benson Jack,
Fritschy JeanMarc
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01506.x
Subject(s) - tropomyosin receptor kinase b , gabaa receptor , postsynaptic potential , inhibitory postsynaptic potential , brain derived neurotrophic factor , biology , neurotrophic factors , microbiology and biotechnology , neurotrophin , gabaergic , neuroscience , neurotransmission , hippocampal formation , receptor , chemistry , biochemistry
Changes in neurotransmitter receptor density at the synapse have been proposed as a mechanism underlying synaptic plasticity. Neurotrophic factors are known to influence synaptic strength rapidly. In the present study, we found that brain‐derived neurotrophic factor (BDNF) acts postsynaptically to reduce γ‐aminobutyric acid (GABA)‐ergic function. Using primary cultures of rat hippocampal neurons, we investigated the effects of BDNF on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and on the localization of GABA A receptors. Application of BDNF (100 ng/mL) led within minutes to a marked reduction (33.5%) of mIPSC amplitudes in 50% of neurons, recorded in the whole‐cell patch‐clamp mode, leaving frequency and decay kinetics unaffected. This effect was blocked by the protein kinase inhibitor K252a, which binds with high affinity to trkB receptors. Immunofluorescence staining with an antibody against trkB revealed that about 70% of cultured hippocampal pyramidal cells express trkB. In dual labelling experiments, use of neurobiotin injections to label the recorded cells revealed that all cells responsive to BDNF were immunopositive for trkB. Treatment of cultures with BDNF reduced the immunoreactivity for the GABA A receptor subunits‐α2, ‐β2,3 and ‐γ2 in the majority of neurons. This effect was detectable after 15 min and lasted at least 12 h. Neurotrophin‐4 (NT‐4), but not neurotrophin‐3 (NT‐3), also reduced GABA A receptor immunoreactivity, supporting the proposal that this effect is mediated by trkB. Altogether the results suggest that exposure to BDNF induces a rapid reduction in postsynaptic GABA A receptor number that is responsible for the decline in GABAergic mIPSC amplitudes.