Summary: Noradrenaline is essential for astrocytes to respond to local stimulation.
Source: VIB Flanders
A collaboration between the laboratories of Vincent Bonin (NERF, supported by VIB, imec and KU Leuven) and Matthew Holt (VIB-KU Leuven Center for Brain & Disease Research) reveals that noradrenaline plays a central role in how astrocytes—star-shaped glial cells closely associated with neurons—process distinct streams of information during behavior. The researchers demonstrate that astrocytes integrate signals about arousal state with local sensory activity in the visual cortex.
The results are published in Current Biology.
Noradrenaline in the brain
Noradrenaline, a neuromodulator released during arousal, is well known for enhancing memory for emotionally relevant events. Past studies focused on its direct effects on neuronal synapses, particularly in regions that handle emotional processing. However, noradrenaline is released broadly throughout the brain and also targets non-neuronal cells such as astrocytes. These glial cells monitor and respond to nearby neuronal activity, but it remained unclear whether astrocytes combine this global arousal signal with specific, local inputs from nearby neural circuits.
Watching astrocytes
To investigate how astrocytes respond to sensory and behavioral inputs, Drs. Michal Slezak and Steffen Kandler used advanced in vivo calcium imaging to monitor astrocyte activity in mouse visual cortex while presenting visual stimuli. The team found that, in moving animals, astrocytes often produced spatially precise responses that tracked the position and movement of visual stimuli across the visual field. These retinotopic responses resembled the expected pattern if astrocytes were reporting local neuronal activity in the visual cortex.
Not every visual presentation evoked an astrocyte response. When the researchers analyzed individual stimulus events, a clear pattern emerged: astrocytic responses were strong when the mouse was in motion but largely absent when the mouse remained still. To test whether noradrenaline mediates this dependence on behavioral state, the team pharmacologically depleted cortical noradrenaline. After depletion, locomotion-related astrocyte activation was essentially abolished and visually driven astrocyte responses were greatly reduced in amplitude, even when stimuli were presented during movement. These findings indicate that noradrenaline is necessary for astrocytes to reliably respond to local sensory stimulation and that astrocytes integrate both local sensory signals and global arousal cues.
Big impact from little-known cells
“Previous research largely concentrated on noradrenaline’s effects on neurons,” says Dr. Slezak. “Our data show that astrocytes can play a much more substantial and nuanced role than previously appreciated.” Dr. Matthew Holt adds that the behavioral-state dependence of astrocyte responses was unexpected: “We now need to determine the molecular mechanisms behind this integration and explore the functional consequences for cortical processing.”
The study highlights two distinct input streams driving astrocyte activity: a diffuse, brain-wide neuromodulatory input associated with locomotion and arousal, and a spatially specific input reflecting local sensory processing. Motor-related activation appears broad and non-selective across cortex, consistent with a neuromodulatory mechanism, whereas visually driven responses are precisely organized and retinotopically mapped during movement. The amplitude of visual responses correlated with pupil size, a proxy for arousal, reinforcing the idea that arousal state modulates sensory-driven astrocyte signaling.
Funding
Support for this work came from several sources. Matthew Holt received funding from the European Research Council (Starting Grant 281961), Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) (Grants 1523014N and 1527315N), and VIB institutional funding. Vincent Bonin was supported by FWO (Grant G0D0516N), the KU Leuven Research Council (Grant C14/16/048), and NERF institutional funding. Michal Slezak received a Marie Curie Intra-European Fellowship (331018).
Source:
VIB Flanders
Media Contacts:
Sooike Stoops – VIB Flanders
Image source:
The image is in the public domain.
Original Research (open access):
“Distinct Mechanisms for Visual and Motor-Related Astrocyte Responses in Mouse Visual Cortex” by Vincent Bonin et al., published in Current Biology (DOI: 10.1016/j.cub.2019.07.078).
Abstract (condensed)
Astrocytes are a prominent cell type in the mammalian brain and display rich calcium signaling that likely influences cellular output. These cells respond to both sensory and motor events, reflecting local neural activity as well as widespread neuromodulatory inputs. Sensory-evoked astrocyte responses are variable, which may be due to interactions between distinct input types. Using calcium imaging during visual stimulation and a treadmill assay, the authors show that motor-related activity produces broad astrocyte activation across cortex, while moving visual stimuli elicit precise, retinotopic astrocyte responses. Visual responses were strongly state-dependent, appearing during locomotion but not during stillness, and their amplitudes correlated with pupil size. Depletion of cortical noradrenaline abolished locomotor responses and attenuated visual responses in amplitude while preserving their spatial organization. These results indicate that cortical astrocytes integrate local sensory information with behavioral state, implicating astrocytes in information processing.