TY - JOUR T1 - Brain-Derived Neurotrophic Factor-Induced Gene Expression Reveals Novel Actions of VGF in Hippocampal Synaptic Plasticity JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10800 LP - 10808 DO - 10.1523/JNEUROSCI.23-34-10800.2003 VL - 23 IS - 34 AU - Janet Alder AU - Smita Thakker-Varia AU - Debra A. Bangasser AU - May Kuroiwa AU - Mark R. Plummer AU - Tracey J. Shors AU - Ira B. Black Y1 - 2003/11/26 UR - http://www.jneurosci.org/content/23/34/10800.abstract N2 - Synaptic strengthening induced by brain-derived neurotrophic factor (BDNF) is associated with learning and is coupled to transcriptional activation. However, identification of the spectrum of genes associated with BDNF-induced synaptic plasticity and the correlation of expression with learning paradigms in vivo has not yet been studied. Transcriptional analysis of BDNF-induced synaptic strengthening in cultured hippocampal neurons revealed increased expression of the immediate early genes (IEGs), c-fos, early growth response gene 1 (EGR1), activity-regulated cytoskeletal-associated protein (Arc) at 20 min, and the secreted peptide VGF (non-acronymic) protein precursor at 3 hr. The induced genes served as prototypes to decipher mechanisms of both BDNF-induced transcription and plasticity. BDNF-mediated gene expression was tyrosine kinase B and mitogen-activated protein kinase-dependent, as demonstrated by pharmacological studies. Single-cell transcriptional analysis of Arc after whole-cell patch-clamp recordings indicated that increased gene expression correlated with enhancement of synaptic transmission by BDNF. Increased expression in vitro predicted elevations in vivo: VGF and the IEGs increased after trace eyeblink conditioning, a hippocampal-dependent learning paradigm. VGF protein was also upregulated by BDNF treatment and was expressed in a punctate manner in dissociated hippocampal neurons. Collectively, these findings suggested that the VGF neuropeptides may regulate synaptic function. We found a novel function for VGF by applying VGF peptides to neurons. C-terminal VGF peptides acutely increased synaptic charge in a dose-dependent manner, whereas N-terminal peptide had no effect. These observations indicate that gene profiling in vitro can reveal new mechanisms of synaptic strengthening associated with learning and memory. ER -