Biology subjects

Wegner, W.

Publications and source records attributed to Wegner, W..

3 recordsLinked to original sources

bioRxiv2023

Pre- and postsynaptic nanostructures increase in size and complexity after LTP induction

Synapses, specialized contact sites between neurons, are the fundamental elements of neuronal information transfer. Synaptic plasticity is related to changes in synaptic morphology and the number of neurotransmitter receptors, and thought to underlie learning and memory. However, it is not clear how these structural and functional changes are connected. We utilized time-lapse super-resolution STED microscopy to visualize structural changes of the synaptic nano-organization of the postsynaptic scaffolding protein PSD95, the presynaptic scaffolding protein Bassoon, and the GluA2 subunit of AMPA receptors by chemically induced long-term potentiation (cLTP) at the level of single synapses. We found that the nano-organization of all three proteins undergoes an increase in complexity and size after cLTP induction. The increase was largely synchronous, peaking at [~]60 min after stimulation. Therefore, both the size and complexity of single pre- and post-synaptic nanostructures serve as substrates for adjusting and determining synaptic strength. Highlights- Time-lapse super-resolution images the structural changes of the PSD95 nano-organization after Cltp - cLTP-induced growth of the PSD95 nano-organization is less than spine head growth and peaks at 60 min, i.e. much slower than the increase in spine volume. - Most PSD95 nanostructures increase in complexity upon cLTP. - Synchronous growth - Nanostructures of pre- and postsynaptic scaffolding proteins and AMPA receptors increase simultaneously and equally strong upon cLTP. - GluA2-containing synaptic AMPA receptors form nanoclusters that increase in size and slightly in number upon cLTP and form subdomains on PSD95. - Bassoon forms complex structures similar to the PSD95 nano-organization.

neuroscience↗

bioRxiv2020

Environmental enrichment enhances precision and remodeling speed of synaptic nanoarchitecture revealed by crosstalk free two-color in vivo STED nanoscopy

Synaptic plasticity underlies long-lasting structural and functional changes to brain circuitry and its experience-dependent remodeling can be fundamentally enhanced by environmental enrichment. It is unknown, however, whether and how environmental enrichment alters the morphology and dynamics of individual synapses. Here, we present a virtually crosstalk free, two-color in vivo STED microscope to simultaneously superresolve the dynamics of endogenous PSD95 of the post-synaptic density and spine geometry. With environmental enrichment, the size distributions of PSD95 and spine head sizes were sharper than in controls, indicating that synaptic strength is set more precisely with environmental enrichment. Spine head geometry and PSD95 assemblies were highly dynamic but their changes correlated only mildly. With environmental enrichment, the topography of the PSD95 nanoorganization was more dynamic; changes in size were smaller than in mice housed in standard cages and depended linearly on their original size. Thus, two-color in vivo time-lapse imaging of synaptic nanoorganization uncovers a unique synaptic nanoplasticity associated with the enhanced learning capabilities under environmental enrichment.

neuroscience↗

bioRxiv2020

Chronic in vivo STED nanoscopy uncovers multiple drivers of shape volatility in stable cortical spines

Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption as well as the storage of long-term information, spines need to be plastic and stable at the same time. Here we advanced in vivo STED nanoscopy to superresolve distinct features of dendritic spines (head size, neck length and width) in mouse neocortex for up to one month. While LTP-dependent changes predict highly correlated modifications of spine geometry, we find both, uncorrelated dynamics, as well as correlated changes, indicating multiple independent drivers of spine remodeling. The magnitude of this remodeling suggests substantial fluctuations in synaptic strength, and is exaggerated in a mouse model of neurodegeneration. Despite this high degree of volatility, all spine features also exhibit persistent components that are maintained over long periods of time. Thus, at the nanoscale, stable dendritic spines exhibit a delicate balance of stability and volatility.

neuroscience↗