PMID- 17267564 OWN - NLM STAT- MEDLINE DCOM- 20070316 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 27 IP - 5 DP - 2007 Jan 31 TI - Endogenous brain-derived neurotrophic factor triggers fast calcium transients at synapses in developing dendrites. PG - 1097-105 AB - Brain-derived neurotrophic factor (BDNF) is involved in many aspects of the formation of functional neuronal networks. BDNF signaling regulates neuronal development not only globally, at the level of entire neurons or networks, but also at a subcellular level and with high temporal specificity; however, the spatiotemporal characteristics of intrinsic BDNF signaling are essentially unknown. Here, we used calcium imaging to directly observe intrinsic BDNF signaling in developing hippocampal neurons. We found that blocking intrinsic BDNF signaling with function-blocking BDNF antibodies (alphaBDNF) or K252-a reduced the frequency of spontaneously occurring fast and localized calcium rises in dendrites. Conversely, focal application of BDNF evoked fast and local dendritic calcium transients, which required activation of TrkB (tropomyosin-related kinase B) receptors as well as activation of voltage-gated sodium and calcium channels. Virus-mediated expression of PSD-95:CFP (postsynaptic density-95 tagged with cyan fluorescent protein) revealed that spontaneous local calcium transients occurred frequently at postsynaptic sites along the dendrite. The frequency of synaptically localized calcium transients was specifically reduced by blocking intrinsic BDNF signaling, whereas nonsynaptic calcium rises were not affected. Furthermore, focal BDNF delivery evoked localized and fast calcium elevations specifically at postsynaptic sites. Together, our results demonstrate that BDNF-dependent calcium signaling in developing hippocampal neurons is fast and occurs at synapses. These temporal and spatial characteristics of intrinsic BDNF signaling as well as its relative abundance renders BDNF an ideal signaling molecule in the establishment of specific synaptic connectivity and functional neuronal networks. FAU - Lang, Susanne B AU - Lang SB AD - Max Planck Institute of Neurobiology, 82152 Martinsried-Munchen, Germany. FAU - Stein, Valentin AU - Stein V FAU - Bonhoeffer, Tobias AU - Bonhoeffer T FAU - Lohmann, Christian AU - Lohmann C LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/metabolism/*physiology MH - Calcium/physiology MH - Calcium Signaling/*physiology MH - Cell Line MH - Dendrites/*physiology MH - Hippocampus/growth & development/metabolism MH - Humans MH - Neurons/metabolism/physiology MH - Organ Culture Techniques MH - Pyramidal Cells/metabolism/physiology MH - Rats MH - Synapses/*physiology PMC - PMC6673203 EDAT- 2007/02/03 09:00 MHDA- 2007/03/17 09:00 PMCR- 2007/07/31 CRDT- 2007/02/03 09:00 PHST- 2007/02/03 09:00 [pubmed] PHST- 2007/03/17 09:00 [medline] PHST- 2007/02/03 09:00 [entrez] PHST- 2007/07/31 00:00 [pmc-release] AID - 27/5/1097 [pii] AID - 3184698 [pii] AID - 10.1523/JNEUROSCI.3590-06.2007 [doi] PST - ppublish SO - J Neurosci. 2007 Jan 31;27(5):1097-105. doi: 10.1523/JNEUROSCI.3590-06.2007.