PMID- 24712995 OWN - NLM STAT- MEDLINE DCOM- 20141218 LR - 20220309 IS - 1460-9568 (Electronic) IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 39 IP - 7 DP - 2014 Apr TI - BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons. PG - 1159-69 LID - 10.1111/ejn.12422 [doi] AB - 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 alpha-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. CI - (c) 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Reimers, Jeremy M AU - Reimers JM AD - Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064-3095, USA. FAU - Loweth, Jessica A AU - Loweth JA FAU - Wolf, Marina E AU - Wolf ME LA - eng GR - DA030844/DA/NIDA NIH HHS/United States GR - K05 DA029099/DA/NIDA NIH HHS/United States GR - R01 DA015835/DA/NIDA NIH HHS/United States GR - DA015835/DA/NIDA NIH HHS/United States GR - F32 DA030844/DA/NIDA NIH HHS/United States GR - R37 DA015835/DA/NIDA NIH HHS/United States GR - DA029099/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, AMPA) RN - Y37615DVKC (Bicuculline) SB - IM MH - Animals MH - Bicuculline/pharmacology MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Excitatory Postsynaptic Potentials MH - Homeostasis MH - Mice MH - Neurons/drug effects/*metabolism/physiology MH - Nucleus Accumbens/cytology/*metabolism MH - Protein Transport MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, AMPA/*metabolism MH - Synaptic Membranes/*metabolism PMC - PMC4410784 MID - NIHMS680279 OTO - NOTNLM OT - co-culture OT - mouse OT - rat OT - receptor trafficking OT - synaptic scaling COIS- The authors declare no conflict of interest. EDAT- 2014/04/10 06:00 MHDA- 2014/12/19 06:00 PMCR- 2015/04/27 CRDT- 2014/04/10 06:00 PHST- 2013/08/16 00:00 [received] PHST- 2013/09/30 00:00 [revised] PHST- 2013/10/12 00:00 [accepted] PHST- 2014/04/10 06:00 [entrez] PHST- 2014/04/10 06:00 [pubmed] PHST- 2014/12/19 06:00 [medline] PHST- 2015/04/27 00:00 [pmc-release] AID - 10.1111/ejn.12422 [doi] PST - ppublish SO - Eur J Neurosci. 2014 Apr;39(7):1159-69. doi: 10.1111/ejn.12422.