We know about neuroplasticity, the brain’s ability to continuously adapt to its environment and experiences. For a decade now, we know that this plasticity also exists at the level of the synapse, the structure through which neurons interact to transmit information. It is thought to be regulated by molecular pathways acquired by human beings throughout evolution. How are they specific to our species, in terms of learning and development? Cécile Charrier, an Inserm researcher, has recently obtained a European Research Council (ERC) Starting Grant in order to elucidate the physiological and pathological roles.
Why is it important to understand the mechanisms that regulate synaptic plasticity?
Since its discovery, it has been shown that synaptic plasticity underlies our adaptive capacities and contributes to the processes of memory and learning. Synaptic plasticity is altered in a large number of brain diseases. Yet it presents particularities in humans that are not found in other mammals or non-human primates. It is useful to decipher the molecular bases of these particularities for a better understanding of what makes the human brain unique. It is also important in order to understand and potentially treat certain neurodevelopmental disorders which only exist in our species.
How did you become interested in synapses?
I studied for my Magister’s degree in biology at the École Normale Supérieure in Paris. There I was lucky to join Antoine Triller's laboratory just when a new single-molecule imaging method was being developed, with which the neurotransmitter receptors inside and outside the synapses can be tracked with nanometric precision. This technique, which today we would qualify as "super-resolution" microscopy because it goes beyond the optical diffraction limit, has truly revolutionized our vision of synapses. It has shown that we are not talking about fixed structures, but dynamic structures whose components are continually being exchanged. I found it fascinating, watching the molecules move within the synapses. And showing that these minuscule changes can have major consequences on how the neurons communicate with each other has been a revelation for me.
What distinguishes our synapses from those of other mammals?
In humans, there are many more synapses, their development is slower, and they can integrate more information. This cannot help but impact the formation of the neural circuits and the transmission of signals in the brain. These particularities are partially based on the influence of genes duplicated only in humans, such as SRGAP2. We have described that the specifically human copy of SRGAP2 increased synaptic density and prolonged their development period. Introducing this gene in mice brings out synaptic particularities specific to humans. This work, which I began during my post-doctoral studies between 2010 and 2013, has served as a foundation for my current work. And it is the progression of this work which has enabled me to obtain European funding.
What prospects does this funding open up for you?
We will be able to develop a project to decipher the regulation mechanisms related to this gene and, more broadly, the molecular pathways linked to human evolution. Our proteomics research indicates that some of these pathways involve proteins implicated in neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. This suggests that regulations existing only in humans could be altered in some neurodevelopmental disorders, that a link exists between human evolution and some brain diseases. That is what we will try to understand by studying the role of these pathways in synaptic development and plasticity. By determining their physiological function, we will be able to improve our understanding of the pathological mechanisms
To find out more about Cécile Charrier’s research
Cécile Charrier is a researcher in the Cellular biology of the synapse team led by Antoine Triller, in Unit 1024 Inserm/CNRS/ENS Paris, at the Biology Institute of the Ecole Normale Supérieure in Paris. She leads the Fundamental mechanisms and human-specific regulations of synaptic development and plasticity research project.