Functional exploration of the astrocytic domain – ASTRODOM

Cerebral communication depends on the transmission of information between neuronal elements at synapses. Such transmission is plastic since its strength can either be potentiated or depressed as an adaptive response to intrinsic and extrinsic changes. As the number of synapses in the brain is huge, the transfer of information at the level of individual synapses cannot be done in an anarchic manner, but rather appropriately in regards to neighboring synapses in a network encoding specific information.

Astrocytes, as neurons’ partners, are ideally positioned to regulate synaptic transmission at the level of neighboring synapses and thus, play a role in this process. First astrocytic processes are in close apposition with the two neuronal elements of synapses. Second, I have shown in my post-doctotal work that astrocytes were regulating the efficacy of transmission at individual synapses. Finally, unlike neurons, astrocytes are organized in anatomical domains independent from each other, each domain containing more than 100 000 synapses. As a consequence, a single astrocyte should be able to detect the activity of all the synapses present in its domain and in turn regulate transmission efficacy. Such a regulation however, is likely to vary as a function of the number of synapses activated. In other words, the astroglial feedback onto an individual synapse is probably influenced by the activity prevailing at neighboring synapses.

Even though considerable progress has been achieved in our understanding of neuron-astrocyte interactions, there are still several key issues that have not been resolved or even tackled. One of them concerns the astrocytic domains. Whether such domains are functional units regulating neighboring synapses and whether such functional domains are independent of each other in function of the network activity remains to be explored. This is the major purpose of my project, which is aimed at exploring astrocytic domains from a functional point of view, under both physiological and pathological conditions.

This young investigator project will have strong impact on our current knowledge of information processing in the brain and thus in Fundamental Neuroscience Research. With a long-term perspective, this basic research will have consequences in Clinical Research considering the involvement of glial cells in human pathologies.