Brain-derived neurotrophic factor silences GABA synapses onto hypothalamic neuroendocrine cells through a postsynaptic dynamin-mediated mechanism.
In the paraventricular nucleus of the hypothalamus (PVN), experimental stress paradigms that suppress gamma-aminobutyric acid (GABA) inputs to parvocellular neuroendocrine cells (PNCs) also increase the expression of brain-derived neurotrophic factor (BDNF). In the adult CNS, BDNF regulates the efficacy of GABAergic transmission, but its contributions to functional changes at inhibitory synapses in the PVN have not been investigated. Analysis of quantal transmission revealed a decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in response to BDNF with no accompanying changes in their amplitude. These effects were completely blocked by prior inclusion of the TrKB receptor antagonist K252a in the patch pipette. Inclusion of a dynamin inhibitory peptide in the patch pipette also blocked the effects of BDNF, consistent with an all-or-none removal of clusters of postsynaptic GABAA receptors. Finally, to confirm a decrease in the availability of postsynaptic GABAA receptors, we tested the effects of BDNF on focal application of the GABAA agonist muscimol. Postsynaptic responses to muscimol were reduced after BDNF. Collectively, these data indicate that BDNF remodels functional synaptic contacts putatively by reducing the surface expression of postsynaptic GABAA receptors.
Hewitt
Sarah A
SA
Hotchkiss Brain Institute and Department of Physiology and Biophysics, University of Calgary, Calgary, Canada T2N 4N1.
Bains
Jaideep S
JS
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D034281:Dynamins / Q000502:physiology*; D004594:Electrophysiology; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D007031:Hypothalamus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009490:Neurosecretory Systems / Q000166:cytology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D018755:GABA Agonists; D026121:Indole Alkaloids; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C049985:staurosporine aglycone; D020813:Receptor, trkB; D034281:Dynamins