A Diversity of Cell Types, Subtypes and Phenotypes in the Central Nervous System: The Importance of Studying Their Complex Relationships

All the cell types in the central nervous system (CNS) cooperate to mediate proper development, function, and plasticity. Similarly, brain repair and neuroprotection, but also demyelination, synaptic loss and neurodegeneration, were increasingly shown to involve non-neuronal cells—both glial cells and peripheral immune cells—among the CNS parenchyma. Adding another degree of complexity, the non-neuronal cell populations are emerging as comprised of different subtypes, endowed with unique properties and functions at steady-state, and which can adopt various phenotypes upon exposure to homeostatic challenges. As a consequence, studying the multidirectional relationships between these different cell types, subtypes and phenotypes in the CNS is now required to provide insights into the mechanisms underlying physiological processes such as neuronogenesis, axon guidance, myelination, vascular formation and remodeling, regulation of neuronal activity, as well as synaptic formation, function and plasticity, and behavioral outputs, among other essential CNS functions.