Signaling by Neuronal Swelling

Fields, R. Douglas

doi:10.1126/scisignal.4155tr1

Cited by 31 publications

(25 citation statements)

References 36 publications

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“…suggesting that perfusion is a potential contributor of the observed dfMRI changes. We further observed that dfMRI activations were mostly located in GM but also had a large component in WM, where swelling has been shown as a mechanism implicated in neuronal transmission (Fields, 2011). Changes in T 2 * appear to have a limited influence on the dfMRI signal, provided that the detected activations were not fully included in those derived from GE-BOLD but rather exhibited an alternative spatial pattern, as suggested by the limited overlap values equal to 45 ± 14%.…”

Section: Discussionmentioning

confidence: 64%

On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm

Luca

Schlaffke

Siero

et al. 2019

Human Brain Mapping

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Diffusion functional magnetic resonance imaging (dfMRI) is a promising technique to map functional activations by acquiring diffusion‐weighed spin‐echo images. In previous studies, dfMRI showed higher spatial accuracy at activation mapping compared to classic functional MRI approaches. However, it remains unclear whether dfMRI measures result from changes in the intracellular/extracellular environment, perfusion, and/or T2 values. We designed an acquisition/quantification scheme to disentangle such effects in the motor cortex during a finger‐tapping paradigm. dfMRI was acquired at specific diffusion weightings to selectively suppress perfusion and free‐water diffusion, then time series of the apparent diffusion coefficient (ADC‐fMRI) and of intravoxel incoherent motion (IVIM) effects were derived. ADC‐fMRI provided ADC estimates sensitive to changes in perfusion and free‐water volume, but not to T2/T2* values. With IVIM modeling, we isolated the perfusion contribution to ADC, while suppressing T2 effects. Compared to conventional gradient‐echo blood oxygenation level‐dependent fMRI, activation maps obtained with dfMRI and ADC‐fMRI had smaller clusters, and the spatial overlap between the three techniques was below 50%. Increases of perfusion fractions were observed during task in both dfMRI and ADC‐fMRI activations. Perfusion effects were more prominent with ADC‐fMRI than with dfMRI but were significant in less than 25% of activation regions. IVIM modeling suggests that the sensitivity to task of dfMRI derives from a decrease of intracellular/extracellular diffusion and an increase of the pseudo‐diffusion signal fraction, leading to different, more confined spatial activation patterns compared to classic functional MRI.

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Section: Discussionmentioning

confidence: 64%

On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm

Luca

Schlaffke

Siero

et al. 2019

Human Brain Mapping

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“…Pioneering work more than 40 years ago provided the first evidence for microscopic swelling of axons during firing of APs (20,21), leading to changes in light reflectivity of brain tissue in response to neuronal activity (22,23). These changes reflect transient osmotic effects caused by the flow of ions and water molecules across the axolemma during AP depolarization and repolarization, where the axonal volume typically recovers quickly after the end of AP firing.…”

Section: Discussionmentioning

confidence: 99%

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity

Chéreau

Saraceno

Angibaud

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

124

118

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Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.STED microscopy | axons | synaptic boutons | action potential conduction velocity | plasticity A xons have long been considered to be static transmission cables, serving to faithfully transmit all-or-none action potentials (APs) over long distances. However, several studies have revealed during the last few years that axon physiology is highly dynamic and regulated (1). It was shown that axons are capable of analog computations (2), undergo activity-dependent structural changes affecting the axonal initial segment (3) and boutons (4), and are subject to local control by astrocytes (5). As these mechanisms can substantially influence AP signaling and synaptic transmission, the computational capability and role of axons in neural circuit function are more complex than previously thought.The conduction of AP along axons imposes widely varying delays on synaptic transmission, and hence shapes the dynamics and timing of signal processing in the brain. In unmyelinated axons, the conduction speed of AP depends crucially on axon diameters (6, 7), which typically vary along the same axon (8), as well as between axons from different cell types (9). However, it is unknown whether axon diameters are dynamic and regulated by activity-dependent mechanisms, which could affect the timing of information transfer between cells and brain areas. This knowledge gap is mostly a result of the inability of conventional light microscopy to resolve thin unmyelinated axons, which can have diameters well below 200 nm, according to electron microscopy studies (10, 11).To overcome this limitation, we applied stimulated emission depletion (STED) microscopy together with electrophysiology in brain slices, ...

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“…High frequency stimulation typically leads to net accumulation of Na + and Cl − and swelling of somata and axonal processes and dendritic spines (see for example [12, 63, 203]). Douglas Fields proposed that in the axonal regions, the activity-dependent swelling may be functionally important for communication between axons and surrounding glial cells, and involve release of neuroactive molecules, presumably via VRAC [62]. Under physiological and supraphysiological conditions, changes in neuronal volume are quite small which make it difficult to differentiate them from changes in the surrounding glial cells.…”

Section: Common and Unique Roles Of Vrac Within The Brainmentioning

confidence: 99%

Volume-regulated anion channel—a frenemy within the brain

Mongin

2015

Pflugers Arch - Eur J Physiol

115

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Volume regulated anion channel (VRAC) is a ubiquitously expressed yet highly enigmatic member of the superfamily of chloride/anion channels. It is activated by cellular swelling and mediates regulatory cell volume decrease in a majority of vertebrate cells, including those in the central nervous system (CNS). In the brain, besides its crucial role in cellular volume regulation, VRAC is thought to play a part in cell proliferation, apoptosis, migration, and release of physiologically active molecules. Although these roles are not exclusive to the CNS, the relative significance of VRAC in the brain is amplified by several unique aspects of its physiology. One important example is contribution of VRAC to release of the excitatory amino acid neurotransmitters, glutamate and aspartate. This latter process is thought to have impact on both normal brain functioning (such as astrocyte-neuron signaling) and neuropathology (via promoting the excitotoxic death of neuronal cells in stroke and traumatic brain injury). In spite of much work in the field the molecular nature of VRAC remained unknown until less than two years ago. Two pioneer publications identified VRAC as the hetero-hexamer formed by the leucine-rich repeat-containing 8 (LRRC8) proteins. These findings galvanized the field and are likely to result in dramatic revisions to our understanding of the place and role of VRAC in the brain, as well as other organs and tissues. The present review briefly recapitulates critical findings in the CNS, and focuses on anticipated impact on the LRRC8 discovery on further progress in neuroscience research.

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Signaling by Neuronal Swelling

Cited by 31 publications

References 36 publications

On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm

On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity

Volume-regulated anion channel—a frenemy within the brain

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