A perspective on astrocyte regulation of neural circuit function and animal behavior

Hirrlinger, Johannes; Nimmerjahn, Axel

doi:10.1002/glia.24168

Cited by 23 publications

(25 citation statements)

References 313 publications

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“…Astrocytes are a heterogeneous population of glial cells which differ in many properties between brain regions, but also within a given area of the brain (Bachoo et al, 2004; Ben Haim & Rowitch, 2017; Farmer & Murai, 2017; Hirrlinger & Nimmerjahn, 2022; Köhler et al, 2021; Matyash & Kettenmann, 2010; Miller, 2018; Oberheim et al, 2012; Schitine et al, 2015; Zhang & Barres, 2010). We here compared metabolic properties of astrocytes in the Ctx and CC, representative brain areas for GM and WM, respectively, focusing on the NADH/NAD + redox state and the cytosolic concentration of ATP.…”

Section: Discussionmentioning

confidence: 99%

Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity

Köhler

Winkler

Junge

et al. 2022

Glia

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Astrocytes are a heterogeneous population of glial cells in the brain, which adapt their properties to the requirements of the local environment. Two major groups of astrocytes are protoplasmic astrocytes residing in gray matter as well as fibrous astrocytes of white matter. Here, we compared the energy metabolism of astrocytes in the cortex and corpus callosum as representative gray matter and white matter regions, in acute brain slices taking advantage of genetically encoded fluorescent nanosensors for the NADH/NAD + redox ratio and for ATP.Astrocytes of the corpus callosum presented a more reduced basal NADH/NAD + redox ratio, and a lower cytosolic concentration of ATP compared to cortical astrocytes. In cortical astrocytes, the neurotransmitter glutamate and increased extracellular concentrations of K + , typical correlates of neuronal activity, induced a more reduced NADH/NAD + redox ratio. While application of glutamate decreased [ATP], K + as well as the combination of glutamate and K + resulted in an increase of ATP levels. Strikingly, a very similar regulation of metabolism by K + and glutamate was observed in astrocytes in the corpus callosum. Finally, strong intrinsic neuronal activity provoked by application of bicuculline and withdrawal of Mg 2+ caused a shift of the NADH/NAD + redox ratio to a more reduced state as well as a slight reduction of [ATP] in gray and white matter astrocytes. In summary, the metabolism of astrocytes in cortex and corpus callosum shows distinct basal properties, but qualitatively similar responses to neuronal activity, probably reflecting the different environment and requirements of these brain regions.

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Section: Discussionmentioning

confidence: 99%

Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity

Köhler

Winkler

Junge

et al. 2022

Glia

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“…Modulation of glia calcium activity during behavior has been observed in a variety of species at different timescales 37 , for example modulation dependent on walking velocity in mice 36, 59 , or integration of behavior over tens of seconds in zebrafish 60 . In head-fixed sleeping flies, a decrease in the fraction of active cells was observed in broad classes of neurons over several minutes 30 .…”

Section: Discussionmentioning

confidence: 99%

“…In mice, calcium imaging in behaving animals was used for investigating sleep regulation in particular with respect to astrocytes 35,36 , and calcium signals in freely walking as well as tethered walking animals depended on sleep or wake states, as well as on sleep deprivation [22][23][24] , without however revealing an exponential dependence on behavioral state as expected of a sleep homeostat.…”

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confidence: 99%

Dynamics of sleep and feeding homeostasis inDrosophilaglia and neurons

Flores-Valle

Seelig

2022

Preprint

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An animal's need to sleep grows with time spent awake and decays again during sleep. In the brain, a homeostatic process or signal has been proposed to represent sleep need, steadily increasing during wakefulness and gradually decreasing during sleep. However, such dynamics of a sleep homeostat, capturing the changing need to sleep in real time depending on behavior, has so far not been observed in identified cells. Here, using a system that we developed for monitoring calcium activity over multiple days in head-fixed, walking fruit flies, we find that a class of glia in the fly brain, called ensheathing glia, shows dynamics expected of a sleep homeostat. Calcium levels in these cells - monitored in a central brain area important for memory, navigation and sleep - integrate activity during wakefulness, reset during sleep, and saturate under sleep deprivation. Optogenetic activation of ensheathing glia induces sleep consistent with charging of the homeostat. The dynamics of the sleep homeostat, observed in glia of different brain compartments with similar but distinct dynamics, agree with conceptual model expectations. Ensheathing glia therefore act as a system for sleep control distributed across brain areas. The structural arrangement of these glia suggests that sleep homeostasis differentially impacts large ensembles of cells at the same time.

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“…Frontiers in Pharmacology frontiersin.org Frontiers in Pharmacology frontiersin.org capable of regulating neuronal circuit functions and animal behavior (Illes et al, 2019;Hirrlinger and Nimmerjahn, 2022).…”

Section: Discussionmentioning

confidence: 99%

ATP indirectly stimulates hippocampal CA1 and CA3 pyramidal neurons via the activation of neighboring P2X7 receptor-bearing astrocytes and NG2 glial cells, respectively

et al. 2022

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There is ongoing dispute on the question whether CNS neurons possess ATP-sensitive P2X7 receptors (Rs) or whether only non-neuronal cells bear this receptor-type and indirectly signal to the neighboring neurons. We genetically deleted P2X7Rs specifically in astrocytes, oligodendrocytes and microglia, and then recorded current responses in neurons to the prototypic agonist of this receptor, dibenzoyl-ATP (Bz-ATP). These experiments were made in brain slice preparations taken from the indicated variants of the P2X7R KO animals. In hippocampal CA3, but not CA1 pyramidal neurons, the deletion of oligodendrocytic (NG2 glial) P2X7Rs abolished the Bz-ATP-induced current responses. In contrast to the Bz-ATP-induced currents in CA3 pyramidal neurons, current amplitudes evoked by the ionotropic glutamate/GABAAR agonists AMPA/muscimol were not inhibited at all. Whereas in the CA3 area NG2 glia appeared to mediate the P2X7R-mediated stimulation of pyramidal neurons, in the CA1 area, astrocytic P2X7Rs had a somewhat similar effect. This was shown by recording the frequencies and amplitudes of spontaneous excitatory currents (sPSCs) in brain slice preparations. Bz-ATP increased the sPSC frequency in CA1, but not CA3 pyramidal neurons without altering the amplitude, indicating a P2X7R-mediated increase of the neuronal input. Micro-injection of the selective astrocytic toxin L-α-aminoadipate into both hippocampi, or the in vitro application of the GABAAR antagonistic gabazine, completely blocked the frequency increases of sPSCs. Hence, CA1 and CA3 pyramidal neurons of the mouse did not possess P2X7Rs, but were indirectly modulated by astrocytic and oligodendrocytic P2X7Rs, respectively.

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A perspective on astrocyte regulation of neural circuit function and animal behavior

Cited by 23 publications

References 313 publications

Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity

Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity

Dynamics of sleep and feeding homeostasis inDrosophilaglia and neurons

ATP indirectly stimulates hippocampal CA1 and CA3 pyramidal neurons via the activation of neighboring P2X7 receptor-bearing astrocytes and NG2 glial cells, respectively

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