Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor.
The homeostatic plasticity hypothesis suggests that neuronal activity scales synaptic strength. This study analyzed effects of activity deprivation on GABAergic synapses in cultured hippocampal neurons using patch clamp electrophysiology to record mIPSCs and immunocytochemistry to visualize presynaptic GAD-65 and the gamma2 subunit of the GABA(A) receptor. When neural activity was blocked for 48 h with tetrodotoxin (TTX, 1 microM), the amplitude of mIPSCs was reduced, corresponding with diminished sizes of GAD-65 puncta and gamma2 clusters. Treatment with the NMDA receptor antagonist APV (50 microM) or the AMPA receptor antagonist DNQX (20 microM) mimicked these effects, and co-application of brain-derived neurotrophic factor (BDNF, 100 ng/mL) overcame them. Moreover, when neurons were treated with BDNF alone for 48 h, these effects were reversed via the TrkB receptor. Overall, these results suggest that activity-dependent scaling of inhibitory synaptic strength can be modulated by BDNF/TrkB-mediated signaling.
Swanwick
Catherine Croft
CC
Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA. swanwickc@nidcd.nih.gov
Murthy
Namita R
NR
Kapur
Jaideep
J
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D005680:gamma-Aminobutyric Acid; D020813:Receptor, trkB; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2