BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons.
Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and in the effects of repeated cocaine exposure. We recently showed that intracranial injection of BDNF into the rat nucleus accumbens (NAc), a key region for cocaine addiction, rapidly increases α-amino-3-hyroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) surface expression. To further characterize BDNF's role in both rapid AMPAR trafficking and slower, homeostatic changes in AMPAR surface expression, we investigated the effects of acute (30 min) and long-term (24 h) treatment with BDNF on AMPAR distribution in NAc medium spiny neurons from postnatal rats co-cultured with mouse prefrontal cortex neurons to restore excitatory inputs. Immunocytochemical studies showed that acute BDNF treatment increased cell surface GluA1 and GluA2 levels, as well as their co-localization, on NAc neurons. This effect of BDNF, confirmed using a protein crosslinking assay, was dependent on ERK but not AKT signaling. In contrast, long-term BDNF treatment decreased AMPAR surface expression on NAc neurons. Based on this latter result, we tested the hypothesis that BDNF plays a role in AMPAR 'scaling down' in response to a prolonged increase in neuronal activity produced by bicuculline (24 h). Supporting this hypothesis, decreasing BDNF signaling with the extracellular BDNF scavenger TrkB-Fc prevented the scaling down of GluA1 and GluA2 surface levels in NAc neurons normally produced by bicuculline. In conclusion, BDNF exerts bidirectional effects on NAc AMPAR surface expression, depending on duration of exposure. Furthermore, BDNF's involvement in synaptic scaling in the NAc differs from its previously described role in the visual cortex.
Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064-3095, USA.
Jeremy M
JM
Reimers
Jessica A
JA
Loweth
Marina E
ME
Wolf
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D006706:Homeostasis; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018091:Receptors, AMPA; D001640:Bicuculline
co-culture; mouse; rat; receptor trafficking; synaptic scaling