Learning, a story about brain plasticity and stabilization

This is a rather difficult piece of research that took me some work to grasp, but very interesting. Throughout our lives, our brains adapt to what we learn and memorize. The brain is made up of complex networks of neurons and synapses that are constantly re-configured, sometimes people than think about brain plasticity. However, in order for learning to leave a trace, connections also must be stabilized. A team researchers from l’Université de Genève has now discovered a new cellular mechanism to help to understand this.

From the press release:

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.

Plasticity and Stability

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 of researchers led by Dominique Muller, Professor in the Department of Fundamental Neuroscience of the Faculty of Medicine at UNIGE, 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,” explained Yann Bernardinelli, the lead author on this study.

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 us to learn and retain memories of what we have learned.

Abstract of the research:

Background: Excitatory synapses in the CNS are highly dynamic structures that can show activity-dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca2+ elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca2+ events in astrocytes and PAP morphological dynamics remain unclear.

Results: In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability.

Conclusions: This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.

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