scholarly journals Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiromu Monai ◽  
Shinnosuke Koketsu ◽  
Yoshiaki Shinohara ◽  
Takatoshi Ueki ◽  
Peter Kusk ◽  
...  

AbstractCortical spreading depolarization (CSD) is a propagating wave of tissue depolarization characterized by a large increase of extracellular potassium concentration and prolonged subsequent electrical silencing of neurons. Waves of CSD arise spontaneously in various acute neurological settings, including migraine aura and ischemic stroke. Recently, we have reported that pan-inhibition of adrenergic receptors (AdRs) facilitates the normalization of extracellular potassium after acute photothrombotic stroke in mice. Here, we have extended that mechanistic study to ask whether AdR antagonists also modify the dynamics of KCl-induced CSD and post-CSD recovery in vivo. Spontaneous neural activity and KCl-induced CSD were visualized by cortex-wide transcranial Ca2+ imaging in G-CaMP7 transgenic mice. AdR antagonism decreased the recurrence of CSD waves and accelerated the post-CSD recovery of neural activity. Two-photon imaging revealed that astrocytes exhibited aberrant Ca2+ signaling after passage of the CSD wave. This astrocytic Ca2+ activity was diminished by the AdR antagonists. Furthermore, AdR pan-antagonism facilitated the normalization of the extracellular potassium level after CSD, which paralleled the recovery of neural activity. These observations add support to the proposal that neuroprotective effects of AdR pan-antagonism arise from accelerated normalization of extracellular K+ levels in the setting of acute brain injury.

2016 ◽  
Vol 37 (5) ◽  
pp. 1626-1633 ◽  
Author(s):  
Jeremy Sword ◽  
Deborah Croom ◽  
Phil L Wang ◽  
Roger J Thompson ◽  
Sergei A Kirov

Spreading depolarization-induced focal dendritic swelling (beading) is an early hallmark of neuronal cytotoxic edema. Pyramidal neurons lack membrane-bound aquaporins posing a question of how water enters neurons during spreading depolarization. Recently, we have identified chloride-coupled transport mechanisms that can, at least in part, participate in dendritic beading. Yet transporter-mediated ion and water fluxes could be paralleled by water entry through additional pathways such as large-pore pannexin-1 channels opened by spreading depolarization. Using real-time in vivo two-photon imaging in mice with pharmacological inhibition or conditional genetic deletion of pannexin-1, we showed that pannexin-1 channels are not required for spreading depolarization-induced focal dendritic swelling.


2021 ◽  
Vol 22 (16) ◽  
pp. 8658
Author(s):  
Azin EbrahimAmini ◽  
Shanthini Mylvaganam ◽  
Paolo Bazzigaluppi ◽  
Mohamad Khazaei ◽  
Alexander Velumian ◽  
...  

A normally functioning nervous system requires normal extracellular potassium ion concentration ([K]o). Throughout the nervous system, several processes, including those of an astrocytic nature, are involved in [K]o regulation. In this study we investigated the effect of astrocytic photostimulation on [K]o. We hypothesized that in vivo photostimulation of eNpHR-expressing astrocytes leads to a decreased [K]o. Using optogenetic and electrophysiological techniques we showed that stimulation of eNpHR-expressing astrocytes resulted in a significantly decreased resting [K]o and evoked K responses. The amplitude of the concomitant spreading depolarization-like events also decreased. Our results imply that astrocytic membrane potential modification could be a potential tool for adjusting the [K]o.


2018 ◽  
Author(s):  
Shuting Han ◽  
Weijian Yang ◽  
Rafael Yuste

To capture the emergent properties of neural circuits, high-speed volumetric imaging of neural activity at cellular resolution is desirable. But while conventional two-photon calcium imaging is a powerful tool to study population activity in vivo, it is restrained to two-dimensional planes. Expanding it to 3D while maintaining high spatiotemporal resolution appears necessary. Here, we developed a two-photon microscope with dual-color laser excitation that can image neural activity in a 3D volume. We imaged the neuronal activity of primary visual cortex from awake mice, spanning from L2 to L5 with 10 planes, at a rate of 10 vol/sec, and demonstrated volumetric imaging of L1 long-range PFC projections and L2/3 somatas. Using this method, we map visually-evoked neuronal ensembles in 3D, finding a lack of columnar structure in orientation responses and revealing functional correlations between cortical layers which differ from trial to trial and are missed in sequential imaging. We also reveal functional interactions between presynaptic L1 axons and postsynaptic L2/3 neurons. Volumetric two-photon imaging appears an ideal method for functional connectomics of neural circuits.


1987 ◽  
Vol 65 (5) ◽  
pp. 1105-1110 ◽  
Author(s):  
B. Moghaddam ◽  
J. O. Schenk ◽  
W. B. Stewart ◽  
A. J. Hansen

Brain ion homeostasis is severely perturbed during spreading depression of Leao and during anoxia. The ionic composition of the extracellular space changes abruptly and approaches the intracellular concentrations owing to an increase in cell permeability. In spreading depression, synchronous transmitter efflux caused by a depolarization of the presynaptic terminals has been implicated as a possible mechanism that would explain the concomitant movement of ions. Anoxia, having many features in common with spreading depression, may follow the same mechanism. We have measured the concentrations of extracellular potassium with ion-selective microelectrodes and dopamine by in vivo voltammetry with carbon fiber microelectrodes during spreading depression and anoxia to compare the temporal relationship between the release of dopamine and ion movements in the striatum. There is a pronounced release of dopamine during both spreading depression and anoxia. In spreading depression, the sharp increase of potassium concentration that follows an initial smaller and slower increase of potassium is accompanied by the release of dopamine. In anoxia, the dopamine release clearly precedes the fast rise of extracellular potassium concentration. We conclude that in striatum, there is a pronounced dopamine release during spreading depression and anoxia, but that the relationships between ionic changes and transmitter release for these two phenomena are different and probably reflect different mechanisms.


2021 ◽  
Author(s):  
Philip J. O’Herron ◽  
David A. Hartmann ◽  
Kun Xie ◽  
Prakash Kara ◽  
Andy Y. Shih

AbstractModulation of brain arteriole diameter is critical for maintenance of cerebral blood pressure and control of hyperemia during regional neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control and monitor blood flow with high spatiotemporal resolution. Here, we describe a new all-optical approach to precisely control and monitor arteriolar contractility in vivo using combined two-photon optogenetics and imaging. The expression of the excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction following brief light pulses. Targeted two-photon activation of ReaCHR using a spatial light modulator (SLM) produced highly localized constrictions when targeted to individual arteries within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient blood flow reductions. Additionally, we show that optogenetic constriction can offset or completely block sensory stimulus evoked vasodilation, providing a valuable tool to dissociate blood flow changes from neural activity.


2019 ◽  
Author(s):  
David Mahringer ◽  
Anders V. Petersen ◽  
Aris Fiser ◽  
Hiroyuki Okuno ◽  
Haruhiko Bito ◽  
...  

Immediate early genes (IEGs) are transcribed in response to neural activity and necessary for many forms of plasticity. However, the dynamics of their expression during learning, as well as their relationship to neural activity, remain unclear. Here we used two-photon imaging in transgenic mice that express a GFP-tagged variant of Arc or c-Fos and a red-shifted calcium indicator to measure learning-related changes in IEG expression levels and neural activity in hippocampal region CA1 as mice learned to perform a two-alternative forced choice task. Neural activity levels correlated positively with IEG expression levelsin vivo. In addition, we found that with learning, a subset of neurons in CA1 increased their responses to the reward-predicting cue, and IEG expression levels early in learning were selectively increased in neurons that would exhibit the strongest learning-related changes. Our findings are consistent with an interpretation of IEG expression levels as markers for experience dependent plasticity.


2016 ◽  
Vol 26 (08) ◽  
pp. 1650044 ◽  
Author(s):  
Lihua Wang ◽  
Suzie Dufour ◽  
Taufik A. Valiante ◽  
Peter L. Carlen

Seizure activity leads to increases in extracellular potassium concentration ([K[Formula: see text]]o), which can result in changes in neuronal passive and active membrane properties as well as in population activities. In this study, we examined how extracellular potassium modulates seizure activities using an acute 4-AP induced seizure model in the neocortex, both in vivo and in vitro. Moderately elevated [K[Formula: see text]]o up to 9[Formula: see text]mM prolonged seizure durations and shortened interictal intervals as well as depolarized the neuronal resting membrane potential (RMP). However, when [K[Formula: see text]]o reached higher than 9[Formula: see text]mM, seizure like events (SLEs) were blocked and neurons went into a depolarization-blocked state. Spreading depression was never observed as the blockade of ictal events could be reversed within 1–2[Formula: see text]min after the raised [K[Formula: see text]]o was changed back to control levels. This concentration-dependent dual effect of [K[Formula: see text]]o was observed using in vivo and in vitro mouse brain preparations as well as in human neocortical tissue resected during epilepsy surgery. Blocking the Ih current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, modulated the elevated [K[Formula: see text]]o influence on SLEs by promoting the high [K[Formula: see text]]o inhibitory actions. These results demonstrate biphasic actions of raised [K[Formula: see text]]o on neuronal excitability and seizure activity.


2020 ◽  
Vol 17 (3) ◽  
pp. 287-290 ◽  
Author(s):  
Jianglai Wu ◽  
Yajie Liang ◽  
Shuo Chen ◽  
Ching-Lung Hsu ◽  
Mariya Chavarha ◽  
...  

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