AstroWars: the return of the astrocytic metabotropic glutamate receptor 5

In the brain, astrocytes express glutamate receptors to detect glutamatergic signalling at synapses. Numerous studies have been conducted to characterize the types and levels of receptor expression, their physiological properties and functional roles. The metabotropic glutamate receptor 5 (mGluR5) is particularly noteworthy. Although it is described as the only classical excitatory metabotropic receptor expressed by astrocytes, recent studies indicate that its expression levels are lower in adulthood compared to the postnatal period. Nevertheless, mGluR5 activation in adulthood remains sufficient to induce robust astrocytic activity. To resolve these seemingly contradictory findings, we review the current understanding of the physiology of astrocytic mGluR5, its expression level variations throughout life, activation consequences and functional roles. In summary, astrocytes maintain sufficient functional levels of mGluR5 throughout life, activation of which triggers Ca²⁺ activity. This activation triggers intracellular processes to modulate synaptic and circuit function, which is relevant due to the extensive glutamatergic signalling in the brain. Moreover, most studies on mGluR5 activation in astrocytes have been conducted using cultured astrocytes or acute brain slices from young rodents. Therefore, further research is needed to investigate the roles of mGluR5 in adulthood, not only in synaptic function but also in behavioural processing. Understanding the regulation of mGluR5 expression levels, physiological properties and functional consequences during adulthood is crucial for fully understanding glutamatergic signalling in brain circuits and its role in the pathophysiology of various neurobiological diseases.