Amazing stuff!
"... Researchers from Janelia and Harvard have now deciphered this conversation, revealing how astrocytes trigger a biochemical circuit that regulates neuronal activity and causes the fish to stop swimming.
While neurotransmitters enable fast communication between individual neurons that lasts milliseconds, neuromodulators like the circuit uncovered in the new work act on populations of neurons to tune neuronal signals over timescales that are more than a thousand times slower, enabling flexible behavior on a timescale of seconds to minutes.
The new work helps to uncover how such neuromodulators reach neurons and unveils a significant role for astroglia in neuromodulation. It also highlights the importance of including information about non-neuronal cells in research into how the brain works. ..."
From the abstract (Perspective):
"It is accepted that neuromodulators such as norepinephrine and dopamine bind to and activate receptors on neurons to influence the activity of neuronal circuits and plasticity (changes in strength or wiring patterns) of synaptic connections, thus shaping the behavior of the organism.
Unlike classical neurotransmitters (e.g., glutamate), which typically mediate fast, point-to-point synaptic communication, neuromodulators diffuse broadly through neural tissue to regulate the strength, duration, and plasticity of neuronal signaling. Emerging evidence now implicates astrocytes—traditionally seen as passive support cells—as active players in neuromodulation (1–3). However, whether astrocytes are necessary intermediaries in neuromodulation or represent regulatory adjuncts to neuronal actions is unclear. On pages 763, 769, and 776 of this issue, Guttenplan et al. (4), Chen et al. (5), and Lefton et al. (6), respectively, address these gaps in knowledge by reporting that astrocytes are indispensable for neuromodulatory signaling across diverse neural circuits, behavioral contexts, and species."
From the editor's summary and abstract:
"Editor’s summary
Astrocytes have been shown to modulate neuronal activity, and dysfunction in neuron-astrocyte communication causes alterations in many cognitive processes. However, the fundamental mechanisms by which astrocytes might be integrated into neuronal circuitry has remained largely unclear.
Three independent studies investigated the mechanisms and molecular players involved in astrocyte-neuron communication using multiple in vivo and in vitro models ...
Guttenplan et al. used fruit fly larvae and mammalian astrocyte cultures to show that exposure to the norepinephrine (NE) homolog tyramine enables astrocytes to suddenly respond potently to a range of neurotransmitters to which they are normally nonresponsive.
In zebrafish, Chen et al. found that NE modulates larval behavior through NE receptor activation on astrocytes, astrocyte secretion of ATP, extracellular metabolism of ATP into adenosine, and activation of neuronal adenosine receptors. Finally, Lefton et al. showed that, in mice, NE modulates synaptic function through a signaling pathway involving astrocytic adrenergic receptors. These three studies point to a model of neural network function in which neuronal signaling and network function can be gated by computations in astrocytes. ...
Abstract
Both neurons and glia communicate through diffusible neuromodulators; however, how neuron-glial interactions in such neuromodulatory networks influence circuit computation and behavior is unclear.
During futility-induced behavioral transitions in the larval zebrafish, the neuromodulator norepinephrine (NE) drives fast excitation and delayed inhibition of behavior and circuit activity.
We found that astroglial purinergic signaling implements the inhibitory arm of this motif. In larval zebrafish, NE triggers astroglial release of adenosine triphosphate (ATP), extracellular conversion of ATP into adenosine, and behavioral suppression through activation of hindbrain neuronal adenosine receptors.
Our results suggest a computational and behavioral role for an evolutionarily conserved astroglial purinergic signaling axis in NE-mediated behavioral and brain state transitions and position astroglia as important effectors in neuromodulatory signaling."
On the sidelines no more: New research shows astrocytes are active players in neuromodulation (original news release)
Astrocytes, hidden puppet masters of the brain (Perspective, no public access)
Norepinephrine changes behavioral state via astroglial purinergic signaling (preprint, open access)
Figure 1. Futility triggers a biphasic behavioral and neural response through NE neuron activation.
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