Glutamate Uptake by Astrocytic Transporters

Astrocytes express glutamate transporters at high density at perisynaptic processes which can tightly control extracellular glutamate levels in proximity of postsynaptic receptors with the potential to modulate functional neuronal activity. Glutamate uptake by these transporters also closely depends on activity-dependent extracellular ion concentrations and may also be regulated by the astrocyte’s intracellular calcium. On the other hand, intracellular \(\mathrm{Ca}^{2+}\) dynamics in the astrocyte too can be modulated by glutamate uptake, with potential for functionally relevant interactions with neural activity. Here, we introduce original modeling arguments to study functional implications of glutamate uptake by astrocytes both on their physiology and on that of neurons. In the first case, we consider the contribution of \(\mathrm{{Na^+}}\) and \(\mathrm{{K^+}}\) homeostasis to astrocytic glutamate uptake, revealing that intracellular anisotropy could account for spatial segregation of transporter- versus receptor-mediated calcium signaling pathways. In the second case, we study how regulation of extracellular glutamate levels by astrocytic transporters could affect tuning responses of primary sensory areas, linking our analysis to experimental observations in the ferret’s primary visual cortex by Schummers et al. (2008, Science 320:1638). We conclude that glutamate uptake by astrocytes can modulate function of neuronal circuits in multiple ways that may look subtle at individual synaptic contacts, but at network level, lead instead to functionally relevant changes in neuronal tuning and stimulus discrimination.