BDNF-induced local protein synthesis and synaptic plasticity in the hippocampus

Cibio Seminar

18 November 2019
Versione stampabile

Date&Time: 18 November 2019 - h. 4:30 pm
Location: Polo Ferrari 2, via Sommarive 9 (Povo) - Room B102

Speaker

  • Carlos B. Duarte - Center for Neuroscience and Cell Biology and Department of Life Sciences, University of Coimbra, Coimbra, Portugal

Abstract:

Brain-derived neurotrophic factor (BDNF) plays important roles in the regulation of neuronal survival and differentiation, functions in activity-dependent plasticity processes at the synaptic level and was shown to be involved in learning and memory formation. This neurotrophin is released to the synapse in an activity-dependent manner and has been shown to activate TrkB receptors located at the pre- and post-synaptic levels. At the presynaptic level BDNF upregulates glutamate release while at the postsynaptic level BDNF induces alterations that enhance the responsiveness of target neurons to the neurotransmitter glutamate released from nerve terminals. Using immunocytochemistry and electrophysiological approaches we and others have found that BDNF enhances the synaptic expression and activity of AMPA and NMDA receptors (NMDAR) for glutamate in cultured hippocampal neurons and in organotypic hippocampal cultures, which contributes to the upregulation of glutamatergic synapses. The effects on NMDAR involve receptors with different subunit compositions (named GluN2A and GluN2B) and is correlated with a decrease in the mobility of the receptor pool present in the synaptic compartment, as determined by tracking single receptors with Quantum dots. Furthermore, the upregulation of synaptic NMDAR induced by BDNF is dependent on the local synthesis of proteins. In this seminar I will discuss the TrkB-induced signaling mechanisms coupled to the regulation of the surface expression of NMDAR and the relevance of hnRNPK, an RNA binding protein involved in the delivery of a large number of transcripts to the dendrites. The transport of hnRNPK along dendrites is regulated by BDNF, and this RNA binding protein is an important mediator of the effects of the neurotrophin in RNA metabolism in the dendritic compartment. The effects of BDNF in local protein synthesis contributes to the input specificity of long-term synaptic potentiation in hippocampal synapses and, together with the effects on protein degradation by the ubiquitin-proteasome system, provide to a tight control of the synaptic proteome in this form of plasticity.