BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA A receptor surface expression

BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA A... 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 GABAA 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 GABAA 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 GABAA 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 GABAA receptor number that is responsible for the decline in GABAergic mIPSC amplitudes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA A receptor surface expression

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Publisher
Wiley
Copyright
Copyright © 2001 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1046/j.0953-816x.2001.01506.x
Publisher site
See Article on Publisher Site

Abstract

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 GABAA 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 GABAA 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 GABAA 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 GABAA receptor number that is responsible for the decline in GABAergic mIPSC amplitudes.

Journal

European Journal of NeuroscienceWiley

Published: Apr 1, 2001

References

  • Neurotrophic factors and their receptors
    Barbacid, Barbacid
  • Fast actions of neurotrophic factors
    Berninger, Berninger; Poo, Poo
  • Neurotrophins and activity‐dependent development of the neocortex
    Bonhoeffer, Bonhoeffer
  • GABAergic mIPSCs in rat cerebellar Purkinje cells are modulated by TrkB and mGluR1‐mediated stimulation of src
    Boxall, Boxall
  • Brain‐derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus
    Frerking, Frerking; Malenka, Malenka; Nicoll, Nicoll
  • Brain‐derived neurotrophic factor alters the synaptic modification threshold in visual cortex
    Huber, Huber; Sawtell, Sawtell; Bear, Bear
  • Physiology of the neurotrophins
    Lewin, Lewin; Barde, Barde
  • Neurotrophins and synaptic plasticity
    McAllister, McAllister; Katz, Katz; Lo, Lo
  • Neurotrophin regulation of synaptic transmission
    Schuman, Schuman

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