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Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl−) is the major central nervous system (CNS) anion mediating inhibitory neurotransmission. Astrocytes are key homoeostatic glial cells populating the CNS, although the role of these cells in regulating excitatory-inhibitory balance remains unexplored. Here we show that astrocytes act as a dynamic Cl− reservoir regulating Cl− homoeostasis in the CNS. We found that intracellular chloride concentration ([Cl−]i) in astrocytes is high and stable during sleep. In awake mice astrocytic [Cl−]i is lower and exhibits large fluctuation in response to both sensory input and motor activity. Optogenetic manipulation of astrocytic [Cl−]i directly modulates neuronal activity during locomotion or whisker stimulation. Astrocytes thus serve as a dynamic source of extracellular Cl− available for GABAergic transmission in awake mice, which represents a mechanism for modulation of the inhibitory tone during sustained neuronal activity. Astrocytes act as a dynamic Cl− reservoir regulating Cl− homeostasis in the CNS. Astrocytic Cl− is high and stable during sleep, it is lower during wakefulness and fluctuates in response to sensory input and motor activity. Efflux of Cl− from astrocytes supports inhibitory transmission in the CNS. [ABSTRACT FROM AUTHOR]

Exogenous kainate receptor agonists have been shown to modulate inhibitory synaptic transmission in the hippocampus, but the pathways involved in physiological activation of the receptors remain largely unknown. Accumulating evidence indicates that astrocytes can release glutamate in a Ca2+dependent manner and signal to neighboring neurons. They tested the hypothesis that astrocyte-derived glutamate activates kainate receptors on hippocampal interneurons. They reported that elevation of intracellular Ca2+ in astrocytes, induced by uncaging Ca2+ o-nitrophenyl-EGTA, increased action potential-driven spontaneous inhibitory postsynaptic currents in nearby interneurons in rat hippocampal slices.

Abstract: A number of studies over the past decade have shown that astrocytes, the supportive cells of the brain, play important roles in synaptic transmission including regulating the strength of both excitatory and inhibitory synapses. A major challenge for the future is to define the role of astrocytes in complex tasks, such as functional hyperemia and sensory processing, as well as their contribution to acute and degenerative diseases of the nervous system. Multiphoton imaging approaches are ideally suited to study electrically non-excitable astrocytes. We here discuss novel in vivo studies aimed at defining the role of astrocytes in normal and pathological brain function. With a better understanding of the role astrocytes play in information processing and regulation of the brain microenvironment in vivo, and the understanding that astrocytes are heavily implicated in the pathology of many diseases such as epilepsy, Alzheimer''s and Parkinson''s diseases, astrocytes provide a promising target for future drug therapy approaches. [Copyright &y& Elsevier]