How the brain stabilizes its connections in order to learn better.

Imaging of PAP Motility around Synapses. (A) z stack projection of confocal images showing CA1 pyramidal neurons infected with SFV(PD)-EGFP-f (red) and stratum radiatum glial cells infected with SFV(A7)-mCherry-f. Scale bar, 100 mm. (B) Top: illustration of a labeled dendritic segment with spines contacted by labeled astrocytes (not shown for clarity; scale bar, 5 mm). This dendritic segment was then 3D reconstructed from serial EM (drawing below). The spines in the dotted square boxes on the dendritic segment are shown below this reconstruction with their neighboring PAPs (green, 1 and 2). Black and white pictures are EM images of the same synapses (intense black: DAB-labeled dendritic segment). On the far right are 3D reconstructions from serial EM showing the same postsynaptic spines (red), terminals (yellow), and PAPs (green) in different orthogonal projections. Scale, 3 mm square boxes. Muller et al 2014.

Throughout a person’s life, their brains adapt to what they learn and memorise. The brain is indeed made up of complex networks of neurons and synapses that are constantly re-configured. However, in order for learning to leave a trace, connections must be stabilized. A team at the University of Geneva (UNIGE) discovered a new cellular mechanism involved in the long-term stabilization of neuron connections, in which non-neuronal cells, called astrocytes, play a role unidentified until now. These results, published in Current Biology, will lead to a better understanding of neurodegenerative and neurodevelopmental diseases.

The central nervous system excitatory synapses, points of contact between neurons that allow them to transmit signals, are highly dynamic structures, which are continuously forming and dissolving. They are surrounded by non-neuronal cells, or glial cells, which include the distinctively star-shaped astrocytes. These cells form complex structures around synapses, and play a role in the transmission of cerebral information which was widely unknown before.

By increasing neuronal activity through whiskers stimulation of adult mice, the scientists were able to observe, in both the somatosensory cortex and the hippocampus, that this increased neuronal activity provokes an increase in astrocytes movements around synapses. The synapses, surrounded by astrocytes, re-organise their architecture, which protects them and increases their longevity.

The team developed new techniques that allowed them to specifically control the different synaptic structures, and to show that the phenomenon took place exclusively in the connections between neurons involved in learning.  In summary, the more the astrocytes surround the synapses, the longer the synapses last, thus allowing learning to leave a mark on memory.

This study identifies a new, two-way interaction between neurons and astrocytes, in which the learning process regulates the structural plasticity of astrocytes, who in turn determine the fate of the synapses. This mechanism indicates that astrocytes apparently play an important role in the processes of learning and memory, which present abnormally in various neurodegenerative and neurodevelopmental diseases, among which Alzheimer’s, autism, or Fragile X syndrome.

This discovery highlights the until now underestimated importance of cells which, despite being non-neuronal, participate in a crucial way in the cerebral mechanisms that allow humans to learn and retain memories of what they have learned.

Source:  The University of Geneva (UNIGE) 

Imaging of PAP Motility around Synapses.  (A) z stack projection of confocal images showing CA1 pyramidal neurons infected with SFV(PD)-EGFP-f (red) and stratum radiatum glial cells infected with SFV(A7)-mCherry-f. Scale bar, 100 mm.  (B) Top: illustration of a labeled dendritic segment with spines contacted by labeled astrocytes (not shown for clarity; scale bar, 5 mm). This dendritic segment was then 3D reconstructed from serial EM (drawing below). The spines in the dotted square boxes on the dendritic segment are shown below this reconstruction with their neighboring PAPs (green, 1 and 2). Black and white pictures are EM images of the same synapses (intense black: DAB-labeled dendritic segment). On the far right are 3D reconstructions from serial EM showing the same postsynaptic spines (red), terminals (yellow), and PAPs (green) in different orthogonal projections. Scale, 3 mm square boxes.  Muller et al 2014.
Imaging of PAP Motility around Synapses. (A) z stack projection of confocal images showing CA1 pyramidal neurons infected with SFV(PD)-EGFP-f (red) and stratum radiatum glial cells infected with SFV(A7)-mCherry-f. Scale bar, 100 mm. (B) Top: illustration of a labeled dendritic segment with spines contacted by labeled astrocytes (not shown for clarity; scale bar, 5 mm). This dendritic segment was then 3D reconstructed from serial EM (drawing below). The spines in the dotted square boxes on the dendritic segment are shown below this reconstruction with their neighboring PAPs (green, 1 and 2). Black and white pictures are EM images of the same synapses (intense black: DAB-labeled dendritic segment). On the far right are 3D reconstructions from serial EM showing the same postsynaptic spines (red), terminals (yellow), and PAPs (green) in different orthogonal projections. Scale, 3 mm square boxes. Muller et al 2014.