Accepted for publication (PostPrint)
European Journal of Neuroscience
Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and 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 AMPA 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 (PFC) 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.
Reimers, Jeremy; Loweth, Jessica; and Wolf, Marina, "BDNF Contributes to Both Rapid and Homeostatic Alterations in AMPA Receptor Surface Expression in Nucleus Accumbens Medium Spiny Neurons" (2014). School of Osteopathic Medicine Faculty Scholarship. 41.
Reimers JM, Loweth JA, Wolf ME. BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons. European Journal of Neuroscience. 2014 Apr;39(7):1159-69. doi: 10.1111/ejn.12422. PMID: 24712995. PMCID: PMC4410784.