Trophic regulation of synaptic plasticity

✍ Scribed by Black, Ira B.

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 238 KB
• Volume: 41
• Category: Article
• ISSN: 0022-3034
• DOI: 10.1002/(sici)1097-4695(199910)41:1<108::aid-neu14>3.0.co;2-u

✦ Synopsis

Trophins are now known to acutely regulate synaptic plasticity, in addition to exerting longrecognized actions on neuronal survival and development. To begin elucidating underlying mechanisms, cultured dissociated hippocampal neurons were examined by whole-cell patch-clamp recording. BDNF (brain derived neurotrophic factor) specifically and selectively increased the integrated synaptic current twofold within five minutes. The effect was mediated postsynaptically by the trkB receptor and intracellular phosphorylationdependent mechanisms. Iontophoresis combined with patch-clamp recording indicated that BDNF increased activity of NMDA (N-methyl-D-aspartate) receptors. Single channel-channel recording indicated that BDNF increased channel open probability by increasing open-ing frequency. In parallel, the trophin specifically increased phosphorylation of NR1 and NR2B subunits of NMDA receptors in the postsynaptic density, providing potential mechanisms eliciting receptor activation. A model is proposed in which activity-driven experience activates specific BDNF gene promoters, leading to enhanced transcription, elevated trophin levels, postsynaptic NMDA receptor activation and increased synaptic transmission. These sequential mechanisms may contribute to enhanced long-term potentiation, a correlate of learning and memory.