High-Frequency Imaging Reveals Synchronised Delta- and Theta-Band Ca2+ Oscillations in the Astrocytic Soma In Vivo.

Abstract

One of the major breakthroughs of neurobiology was the identification of distinct ranges of oscillatory activity in the neuronal network that were found to be responsible for specific biological functions, both physiological and pathological in nature. Astrocytes, physically coupled by gap junctions and possessing the ability to simultaneously modulate the functions of a large number of surrounding synapses, are perfectly positioned to introduce synchronised oscillatory activity into the neural network. However, astrocytic somatic calcium signalling has not been investigated to date in the frequency ranges of common neuronal oscillations, since astrocytes are generally considered to be slow responders in terms of Ca2+ signalling. Using high-frequency two-photon imaging, we reveal fast Ca2+ oscillations in the soma of astrocytes in the delta (0.5-4 Hz) and theta (4-8 Hz) frequency bands in vivo in the rat cortex under ketamine-xylazine anaesthesia, which is known to induce permanent slow-wave sleep. The high-frequency astrocytic Ca2+ signals were not observed under fentanyl anaesthesia, excluding the possibility that the signals were introduced by motion artefacts. We also demonstrate that these fast astrocytic Ca2+ signals, previously considered to be exclusive to neurons, are present in a large number of astrocytes and are phase synchronised at the astrocytic network level. We foresee that the disclosure of these high-frequency astrocytic signals may help with understanding the appearance of synchronised oscillatory signals and may open up new avenues of treatment for neurological conditions characterised by altered neuronal oscillations.