Astrocytes are complex glial cells that play many essential roles in the brain, including the fine-tuning of synaptic activity and blood flow. These roles are linked to fluctuations in intracellular Ca2+ within astrocytes. Recent advances in imaging techniques have identified localized Ca2+ transients within the fine processes of the astrocytic structure, which we term microdomain Ca2+ events. These Ca2+ transients are very diverse and occur under different conditions, including in the presence or absence of surrounding circuit activity. This complexity suggests that different signalling mechanisms mediate microdomain events which may then encode specific astrocyte functions from the modulation of synapses up to brain circuits and behaviour. Several recent studies have shown that a subset of astrocyte microdomain Ca2+ events occur rapidly following local neuronal circuit activity. In this review, we consider the physiological relevance of microdomain astrocyte Ca2+ signalling within brain circuits and outline possible pathways of extracellular Ca2+ influx through ionotropic receptors and other Ca2+ ion channels, which may contribute to astrocyte microdomain events with potentially fast dynamics.

Cortical astrocytes encode sensory information through their calcium dynamics, but it remains unclear if modulation of astrocyte calcium transients can change somatosensory circuits and behaviour in vivo. Here, we used a novel knockdown approach to selectively reduce astrocyte N-methyl-D-aspartate receptors (NMDAR). We found that these ionotropic receptors contribute to astrocyte Ca2+transients encoding sensory information. This was essential for the optimal processing of sensory information in nearby neurons, since a reduction in astrocyte NMDARs caused circuit dysfunction and impaired neuronal responses to stimulation. This led to sensory discrimination deficits in the animal. Overall, our findings show that astrocytes can rapidly respond to glutamatergic transmission via their NMDAR and these receptors are an important component for astrocyte-neuron interactions that regulate cortical sensory discrimination in vivo.

Early life adversity (ELA) causes aberrant functioning of neural circuits affecting the health of an individual. While ELA-induced behavioural disorders resulting from sensory and cognitive disabilities can be assessed clinically, the neural mechanisms need to be probed using animal models by employing multi-pronged experimental methods. As ELA can alter perception, we investigated the effect of early weaning on murine olfaction. By implementing go/no-go odour discrimination paradigm, we observed olfactory learning and memory impairments in early life stressed (ELS) male mice. As olfactory bulb (OB) circuitry plays a critical role in odour learning, we studied the plausible changes in the OB of ELS mice. Lowered c-Fos activity in the external plexiform layer and a reduction in the number of dendritic processes of somatostatin-releasing, GABAergic interneurons (SOM-INs) in the ELS mice led us to hypothesize the underlying circuit. We recorded reduced synaptic inhibitory feedback on mitral/tufted (M/T) cells, in the OB slices from ELS mice, explaining the learning deficiency caused by compromised refinement of OB output. The role of SOM-INs was revealed by learning-dependent refinement of Ca2+ dynamics quantified by GCaMP6f signals. Further, the causal role of SOM-INs involving circuitry was investigated by optogenetic bi-directional modulation during odour discrimination learning. Photo-activating these neurons rescued ELA-induced learning deficits. Conversely, photo-inhibition caused learning deficiency in control animals, while it completely abolished the learning in ELS mice, confirming the adverse effects mediated by SOM-INs. Our results thus establish the role of specific inhibitory circuit in pre-cortical sensory area in orchestrating ELAdependent changes.