Local Resting Ca2+ Controls the Scale of Astroglial Ca2+ Signals

Astroglia regulate neurovascular coupling while engaging in signal exchange with neurons. The underlying cellular machinery is thought to rely on astrocytic Ca2+ signals, but what controls their amplitude and waveform is poorly understood. Here, we employ time-resolved two-photon excitation fluorescence imaging in acute hippocampal slices and in cortex in vivo to find that resting [Ca2+] predicts the scale (amplitude) and the maximum (peak) of astroglial Ca2+ elevations. We bidirectionally manipulate resting [Ca2+] by uncaging intracellular Ca2+ or Ca2+ buffers and use ratiometric imaging of a genetically encoded Ca2+ indicator to establish that alterations in resting [Ca2+] change co-directionally the peak level and anti-directionally the amplitude of local Ca2+ transients. This relationship holds for spontaneous and for induced (for instance by locomotion) Ca2+ signals. Our findings uncover a basic generic rule of Ca2+ signal formation in astrocytes, thus also associating the resting Ca2+ level with the physiological “excitability” state of astroglia

Astrocytes in memory formation and maintenance

Learning and memory are fundamental but highly complex functions of the brain. They rely on multiple mechanisms including the processing of sensory information, memory formation, maintenance of short- and long-term memory, memory retrieval and memory extinction. Recent experiments provide strong evidence that, besides neurons, astrocytes crucially contribute to these higher brain functions. However, the complex interplay of astrocytes and neurons in local neuron–glia assemblies is far from being understood. Although important basic cellular principles that govern and link neuronal and astrocytic cellular functions have been established, additional mechanisms clearly continue to emerge. In this short essay, we first review current technologies allowing the experimenter to explore the role of astrocytes in behaving animals, with focus on spatial memory. We then discuss astrocytic signaling mechanisms and their role in learning and memory. We also reveal gaps in our knowledge that currently prevent a comprehensive understanding of how astrocytes contribute to acquisition, storage and retrieval of memory by modulating neuronal signaling in local circuits