Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity.

Ulyana Lalo,Alexander Bogdanov,Yuriy Pankratov,Guy W Moss

doi:10.3390/brainsci10070462

Abstract

Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release BDNF via a calcium-dependent mechanism. To elucidate a role for astroglia-derived BDNF in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the BDNF/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused BDNF-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca2+ signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of BDNF is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain.

Highlights

The ability of the brain to adapt to environmental and biochemical challenges during development and aging strongly depends on the capability of synapses to scale their strength in response to the activity of neighbouring neuronal networks [1,2,3]
We have shown previously that mitogen and stress-activated kinase 1 (MSK1) protein kinase is instrumental for the Brain-derived neurotrophic factor (BDNF)-mediated homeostatic synaptic scaling and the effects of environmental enrichment (EE) on excitatory synapses in the hippocampus [9,12]
Did not lead to marked changes in the miniature spontaneous synaptic currents (mEPSCs) frequency (Figure 1C). These results demonstrate that glia-induced BDNF-dependent homeostatic synaptic scaling occurs mainly via postsynaptic mechanisms, to previously reported forms of homeostatic synaptic plasticity [9]

Summary

Introduction

The ability of the brain to adapt to environmental and biochemical challenges during development and aging strongly depends on the capability of synapses to scale their strength in response to the activity of neighbouring neuronal networks [1,2,3]. Such form of responsiveness of synapses, conventionally termed as a homeostatic synaptic plasticity [2], has been implicated in the potential beneficial effects of exercise and active lifestyle on cognitive function [4,5,6,7,8]. We have shown previously that MSK1 protein kinase is instrumental for the BDNF-mediated homeostatic synaptic scaling and the effects of environmental enrichment (EE) on excitatory synapses in the hippocampus [9,12]

Results

Discussion

Conclusion