Visualizing BDNF cell-to-cell transfer and its effects on synapse and circuit function
Final Report Abstract
Brain-derived neurotrophic factor (BDNF) is essential for neuronal growth, differentiation, and synaptic strengthening. The release of BDNF from neurons, and the effects of BDNF on neurons, have both been well-studied separately, where transfer of BDNF from neurons to other neurons has been assumed. However, the transfer of BDNF to different cell types has not been well-characterized. Using a four-fluorophore imaging approach to identify the cell of origin and target cells, we quantified the transfer of BDNF from neurons to other cells. We found that astrocytes are the main recipient of neuronally expressed mature BDNF. Overexpression of the TrkB receptor in neurons redirected released BDNF from astrocytes to neurons, suggesting that TrkB levels determine neuronal versus astrocytic BDNF uptake. Increased neuronal activity further increased astrocytic (but not neuronal) uptake of neuronally expressed BDNF. We further discovered that the BDNF taken up by astrocytes increases astrocytic territory, which may support neuron and synapse number and circuit strength. Using astrocyte-specific TrkB.T1 knockout cultures, we found that uptake of BDNF by astrocytes is mediated by the TrkB.T1 receptor. Transfer of BDNF from neurons to astrocytes in the hippocampus may support hippocampal circuit function. In the striatum, BDNF transferred from cortical neurons to astrocytes may support medium spiny neurons and striatal circuit function.
Publications
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Visualizing BDNF cell-to-cell transfer reveals astrocytes are the primary recipient of neuronal BDNF. Cold Spring Harbor Laboratory.
Stahlberg, Markus A.; Kügler, Sebastian & Dean, Camin
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The diversity of synaptotagmin isoforms. Current Opinion in Neurobiology, 63, 198-209.
Wolfes, Anne C. & Dean, Camin
