Distinct Mechanisms for Visual and Motor-Related Astrocyte Responses in Mouse Visual Cortex

Abstract

SummaryAstrocytes are a major cell type in the mammalian nervous system, are in close proximity to neurons, and show rich Ca2+ activity thought to mediate cellular outputs. Astrocytes show activity linked to sensory [1, 2] and motor [3, 4] events, reflecting local neural activity and brain-wide neuromodulatory inputs. Sensory responses are highly variable [5, 6, 7, 8, 9, 10], which may reflect interactions between distinct input types [6, 7, 9]. However, the diversity of inputs generating astrocyte activity, particularly during sensory stimulation and behavior, is not fully understood [11, 12]. Using a combination of Ca2+ imaging, a treadmill assay, and visual stimulation, we examined the properties of astrocyte activity in mouse visual cortex associated with motor or sensory events. Consistent with previous work, motor activity activated astrocytes across the cortex with little specificity, reflecting a diffuse neuromodulatory mechanism. In contrast, moving visual stimuli generated specific activity patterns that reflected the stimulus' trajectory within the visual field, precisely as one would predict if astrocytes reported local neural activity. Visual responses depended strongly on behavioral state, with astrocytes showing high amplitude Ca2+ transients during locomotion and little activity during stillness. Furthermore, the amplitudes of visual responses were highly correlated with pupil size, suggesting a role of arousal. Interestingly, while depletion of cortical noradrenaline abolished locomotor responses, visual responses were only reduced in amplitude and their spatiotemporal organization remained intact, suggesting two distinct types of inputs underlie visual responses. We conclude that cortical astrocytes integrate local sensory information and behavioral state, suggesting a role in information processing.

FKBP5 polymorphisms induce differential glucocorticoid responsiveness in primary CNS cells – First insights from novel humanized mice

“…Besides their supportive role in terms of metabolism, astrocytes were shown to influence information processing and cognition by integrating local sensory information and behavioral state (Hallmann et al., 2017; Lima et al., 2014; Oksanen et al., 2019; Peteri et al., 2019; Slezak et al., 2019). In response to glucocorticoids, resetting of the circadian clock via non‐canonical pathways (Suchmanova et al., 2019) was reported.…”

No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience

“…Cortical astrocytes show differential responses to the metabotropic agonist phenylephrine, which reflect the distribution of morphologically and transcriptomically distinct astrocyte populations [63]. Finally, work from our own lab suggests that local synaptic activity as well as the behavioral state of the animal are crucial in shaping intracellular Ca 2+ signaling in the mouse visual cortex, suggesting that astrocytes act as signal integrators to produce distinct physiological effects [82]. This is in agreement with previous work showing the effects of the neuromodulator noradrenaline on astrocyte signaling [91].…”

“…Recent studies, however, have taken advantage of the fact that genetically encoded calcium indicators (GECIs) can be expressed in a cell type specific manner and targeted to specific subcellular locations. They have revealed a rich diversity of Ca 2+ signals in cells, ranging from the generation of signaling microdomains [79][80][81] through to global waves that encompass entire astrocytes, including their cell bodies [81,82]. Ca 2+ responses may be spontaneous [79,83] or evoked by neuronal activity [25,26], with differences between brain regions reported; striatal and hippocampal astrocytes show differences in these two forms of Ca 2+ signal [15].…”

Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia

“…Recent evidences highlight important roles of astroglia in regulating neural activity, brain states, and animal behavior, both in vertebrates (Brancaccio, Patton, Chesham, Maywood, & Hastings, 2017) and invertebrates (Ma, Stork, Bergles, & Freeman, 2016). Studies in rodents showed that astroglial cells are highly dynamic components of the brain, which respond to locomotion (Nimmerjahn, Mukamel, & Schnitzer, 2009; Sekiguchi et al, 2016; Slezak et al, 2019) or sensory stimulation (Gu et al, 2018; Slezak et al, 2019) with prominent changes in astroglial calcium levels and can regulate learning (Adamsky et al, 2018; Corkrum et al, 2020) or other state transitions (Bojarskaite et al, 2019; Cui et al, 2018; Oe et al, 2020; Poskanzer & Yuste, 2016) in the brain. Norepinephrine (Bekar, He, & Nedergaard, 2008; Oe et al, 2020; Salm & McCarthy, 1990; Shao & McCarthy, 1997) and acetylcholine (Araque, Martin, Perea, Arellano, & Buno, 2002; Pabst et al, 2016; Takata et al, 2011) are proposed to be the primary triggers for activating astroglia, yet several other molecules including glutamate (Hamilton et al, 2008; Mothet et al, 2005; Sun et al, 2013) play prominent roles in astroglial physiology.…”