Cortex-wide Changes in Extracellular Potassium Ions Parallel Brain State Transitions in Awake Behaving Mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Rasmussen R
PROVIDER: S-EPMC6790006 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Cortex-wide Changes in Extracellular Potassium Ions Parallel Brain State Transitions in Awake Behaving Mice.
Rasmussen Rune R Nicholas Eric E Petersen Nicolas Caesar NC Dietz Andrea Grostøl AG Xu Qiwu Q Sun Qian Q Nedergaard Maiken M
Cell reports 20190701 5
Brain state fluctuations modulate sensory processing, but the factors governing state-dependent neural activity remain unclear. Here, we tracked the dynamics of cortical extracellular K<sup>+</sup> concentrations ([K<sup>+</sup>]<sub>o</sub>) during awake state transitions and manipulated [K<sup>+</sup>]<sub>o</sub> in slices, during visual processing, and during skilled motor execution. When mice transitioned from quiescence to locomotion, [K<sup>+</sup>]<sub>o</sub> increased by 0.6-1.0 mM in ...[more]
Similar Datasets
Project description:The subthreshold mechanisms that underlie neuronal correlations in awake animals are poorly understood. Here, we perform dual whole-cell recordings in the visual cortex (V1) of awake mice to investigate membrane potential (Vm) correlations between upper-layer sensory neurons. We find that the membrane potentials of neighboring neurons display large, correlated fluctuations during quiet wakefulness, including pairs of cells with disparate tuning properties. These fluctuations are driven by correlated barrages of excitation followed closely by inhibition (?5-ms lag). During visual stimulation, low-frequency activity is diminished, and coherent high-frequency oscillations appear, even for non-preferred stimuli. These oscillations are generated by alternating excitatory and inhibitory inputs at a similar lag. The temporal sequence of depolarization for pairs of neurons is conserved during both spontaneous- and visually-evoked activity, suggesting a stereotyped flow of activation that may function to produce temporally precise "windows of opportunity" for additional synaptic inputs.
| S-EPMC6224163 | biostudies-literature
Project description:Macroscopic (millimeter scale) functional clustering is a hallmark characteristic of motor cortex spatial organization in awake behaving mammals; however, almost no information is known about the functional micro-organization (approximately 100 microm scale). Here, we optically recorded intracellular calcium transients of layer 2/3 neurons with cellular resolution over approximately 200-microm-diameter fields in the forelimb motor cortex of mobile, head-restrained mice during two distinct movements (running and grooming). We showed that the temporal correlation between neurons was statistically larger the closer the neurons were to each other. We further explored this correlation by using two separate methods to spatially segment the neurons within each imaging field: K-means clustering and correlations between single neuron activity and mouse movements. The two methods segmented the neurons similarly and led to the conclusion that the origin of the inverse relationship between correlation and distance seen statistically was twofold: clusters of highly temporally correlated neurons were often spatially distinct from one another, and (even when the clusters were spatially intermingled) within the clusters, the more correlated the neurons were to each other, the shorter the distance between them. Our results represent a direct observation of functional clustering within the microcircuitry of the awake mouse motor cortex.
| S-EPMC2872549 | biostudies-literature
Project description:BackgroundOur understanding of the neural circuits controlling micturition and continence is constrained by a paucity of techniques for measuring voiding in awake, behaving mice.New methodTo facilitate progress in this area, we developed a new, non-invasive assay, micturition video thermography (MVT), using a down-facing thermal camera above mice on a filter paper floor.ResultsMost C57B6/J mice void infrequently, with a stereotyped behavioral sequence, and usually in a corner. The timing of each void is indicated by the warm thermal contrast of freshly voided urine. Over the following 10-15?min, urine cools to ?3?°C below the ambient temperature and spreads radially in the filter paper. By measuring the area of cool contrast comprising this "thermal void spot," we can derive the initially voided volume. Thermal videos also reveal mouse behaviors including a home-corner preference apart from void spots, and a stereotyped, seconds-long pause while voiding.Comparison with existing methods and conclusionsMVT is a robust, non-invasive method for measuring the timing, volume, and location of voiding. It improves on an existing technique, the void spot assay, by adding timing information, and unlike the cystometrogram preparation, MVT does not require surgical catheterization. Combining MVT with current neuroscience techniques will improve our understanding of the neural circuits that control continence, which is important for addressing the growing number of patients with urinary incontinence as the population ages.
| S-EPMC6942227 | biostudies-literature
Project description:Thousands of functional magnetic resonance imaging (fMRI) studies have provided important insight into the human brain. However, only a handful of these studies tested infants while they were awake, because of the significant and unique methodological challenges involved. We report our efforts to address these challenges, with the goal of creating methods for awake infant fMRI that can reveal the inner workings of the developing, preverbal mind. We use these methods to collect and analyze two fMRI datasets obtained from infants during cognitive tasks, released publicly with this paper. In these datasets, we explore and evaluate data quantity and quality, task-evoked activity, and preprocessing decisions. We disseminate these methods by sharing two software packages that integrate infant-friendly cognitive tasks and eye-gaze monitoring with fMRI acquisition and analysis. These resources make fMRI a feasible and accessible technique for cognitive neuroscience in awake and behaving human infants.
| S-EPMC7481790 | biostudies-literature
Project description:Lower limb paralysis from spinal cord injury (SCI) or neurological disease carries a poor prognosis for recovery and remains a large societal burden. Neurophysiological and neuroprosthetic research have the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable nonhuman primate model for paraplegia hinders their advancement. Therefore, our multidisciplinary team developed a way to induce temporary paralysis in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for sensorimotor blockade. During treadmill walking, aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously injected into the ports of three rhesus macaques while surface electromyography (EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60-90 min in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards, and the ports remained functional after several months. This technique will enable recording from the cortex and/or spinal cord in awake behaving nonhuman primates during the onset, maintenance, and resolution of paraplegia for the first time, thus opening the door to answering basic neurophysiological questions about the acute neurological response to spinal cord injury and recovery. It will also negate the need to permanently injure otherwise high-value research animals for certain experimental paradigms aimed at developing and testing neural interface decoding algorithms for patients with lower extremity dysfunction.NEW & NOTEWORTHY A novel implantable lumbar epidural catheter-subcutaneous port system enables targeted drug delivery and induction of temporary paraplegia in awake, behaving nonhuman primates. Three macaques displayed loss of voluntary leg movement for 60-90 min after injection of lidocaine with epinephrine, followed by a full recovery. This technique for the first time will enable ethical live recording from the proximal central nervous system during the acute onset, maintenance, and resolution of paraplegia.
| S-EPMC5596146 | biostudies-literature
Project description:Channelrhodopsin2 (ChR2) optogenetic excitation is widely used to study neurons, astrocytes, and circuits. Using complementary approaches in situ and in vivo, we found that ChR2 stimulation leads to significant transient elevation of extracellular potassium ions by ∼5 mM. Such elevations were detected in ChR2-expressing mice, following local in vivo expression of ChR2(H134R) with adeno-associated viruses (AAVs), in different brain areas and when ChR2 was expressed in neurons or astrocytes. In particular, ChR2-mediated excitation of striatal astrocytes was sufficient to increase medium spiny neuron (MSN) excitability and immediate early gene expression. The effects on MSN excitability were recapitulated in silico with a computational MSN model and detected in vivo as increased action potential firing in awake, behaving mice. We show that transient, physiologically consequential increases in extracellular potassium ions accompany ChR2 optogenetic excitation. This coincidental effect may be important to consider during astrocyte studies employing ChR2 to interrogate neural circuits and animal behavior.
| S-EPMC6582980 | biostudies-literature
Project description:A longstanding goal in neuroscience has been to image membrane voltage across a population of individual neurons in an awake, behaving mammal. Here we describe a genetically encoded fluorescent voltage indicator, SomArchon, which exhibits millisecond response times and is compatible with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable several-fold over previously published fully genetically encoded reagents1-8. Under conventional one-photon microscopy, SomArchon enables the routine population analysis of around 13 neurons at once, in multiple brain regions (cortex, hippocampus, and striatum) of head-fixed, awake, behaving mice. Using SomArchon, we detected both positive and negative responses of striatal neurons during movement, as previously reported by electrophysiology but not easily detected using modern calcium imaging techniques9-11, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examined how spikes relate to the subthreshold theta oscillations of individual hippocampal neurons, with SomArchon showing that the spikes of individual neurons are more phase-locked to their own subthreshold theta oscillations than to local field potential theta oscillations. Thus, SomArchon reports both spikes and subthreshold voltage dynamics in awake, behaving mice.
| S-EPMC6858559 | biostudies-literature
Project description:Life threatening fear after a single exposure evolves in a subset of vulnerable individuals to anxiety, which may persist for their lifetime. Yet neither the whole brain's response to innate acute fear nor how brain activity evolves over time is known. Sustained neuronal activity may be a factor in the development of a persistent fear response. We couple two experimental protocols to provoke acute fear leading to prolonged fear: Predator stress (PS), a naturalistic approach to induce fear in rodents; and Serotonin transporter knockout mouse (SERT-KO) that responds to PS with sustained defensive behavior. Behavior was monitored before, during and at short and long times after PS in wild type (WT) and SERT-KO mice. Both genotypes responded to PS with defensive behavior. SERT-KO retained defensive behavior for 23 days, while WT mice returned to baseline exploratory behavior by 9 days. Thus, differences in neural activity between WT and SERT-KO 9 days after PS identifies neural correlates of persistent defensive behavior, in mice. We used longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) to identify brain-wide neural activity associated with different behaviors. Mn2+ accumulation in active neurons occurs in awake, behaving mice and is retrospectively imaged. Following the same two cohorts of mice, WT and SERT-KO, longitudinally allowed unbiased quantitative comparisons of brain-wide activity by statistical parametric mapping (SPM). During natural behavior in WT, only low levels of activity-induced Mn2+-accumulation were detected, while much more accumulation appeared immediately after PS in both WT and SERT-KO, and evolved at 9 days to a new activity pattern (p < 0.0001, uncorr., T = 5.4). Patterns of accumulation differed between genotypes, with more regions of the brain and larger volumes within regions involved in SERT-KO than WT. A new computational segmentation analysis, using our InVivo Atlas based on a manganese-enhanced MR image of a living mouse, revealed dynamic changes in the volume of significantly enhanced voxels within each segment that differed between genotypes across 45 of 87 segmented regions. At Day 9 after PS, the striatum and ventral pallidum were active in both genotypes but more so in the SERT-KO. SERT-KO also displayed sustained or increased volume of Mn2+ accumulations between Post-Fear and Day 9 in eight segments where activity was decreased or silenced in WT. C-fos staining, an alternative neural activity marker, of brains from the same mice fixed at conclusion of imaging sessions confirmed that MEMRI detected active neurons. Intensity measurements in 12 regions of interest (ROIs) supported the SPM results. Between group comparisons by SPM and of ROI measurements identified specific regions differing between time points and genotypes. We report brain-wide activity in response to a single exposure of acute fear, and, for the first time, its evolution to new activity patterns over time in individuals vulnerable to persistent fear. Our results show multiple regions with dynamic changes in neural activity and that the balance of activity between segments is disordered in the SERT-KO. Thus, longitudinal MEMRI represents a powerful approach to discover how brain-wide activity evolves from the natural state either after an experience or during a disease process.
| S-EPMC7805483 | biostudies-literature
Project description:Animal-fMRI is a powerful method to understand neural mechanisms of cognition, but it remains a major challenge to scan actively participating small animals under low-stress conditions. Here, we present an event-related functional MRI platform in awake pigeons using single-shot RARE fMRI to investigate the neural fundaments for visually-guided decision making. We established a head-fixated Go/NoGo paradigm, which the animals quickly learned under low-stress conditions. The animals were motivated by water reward and behavior was assessed by logging mandibulations during the fMRI experiment with close to zero motion artifacts over hundreds of repeats. To achieve optimal results, we characterized the species-specific hemodynamic response function. As a proof-of-principle, we run a color discrimination task and discovered differential neural networks for Go-, NoGo-, and response execution-phases. Our findings open the door to visualize the neural fundaments of perceptual and cognitive functions in birds-a vertebrate class of which some clades are cognitively on par with primates.
| S-EPMC7501281 | biostudies-literature
Project description:Kv7.1 (KCNQ1) channels are regulators of several physiological processes including vasodilatation, repolarization of cardiomyocytes, and control of secretory processes. A number of Kv7.1 pore mutants are sensitive to extracellular potassium. We hypothesized that extracellular potassium also modulates wild-type Kv7.1 channels. The Kv7.1 currents were measured in Xenopus laevis oocytes at different concentrations of extracellular potassium (1-50 mM). As extracellular potassium was elevated, Kv7.1 currents were reduced significantly more than expected from theoretical calculations based on the Goldman-Hodgkin-Katz flux equation. Potassium inhibited the steady-state current with an IC(50) of 6.0 ± 0.2 mM. Analysis of tail-currents showed that potassium increased the fraction of channels in the inactivated state. Similarly, the recovery from inactivation was slowed by potassium, suggesting that extracellular potassium stabilizes an inactivated state in Kv7.1 channels. The effect of extracellular potassium was absent in noninactivating Kv7.1/KCNE1 and Kv7.1/KCNE3 channels, further supporting a stabilized inactivated state as the underlying mechanism. Interestingly, coexpression of Kv7.1 with KCNE2 did not attenuate the inhibition by potassium. In a number of other Kv channels, including Kv1.5, Kv4.3, and Kv7.2-5 channels, currents were only minimally reduced by an increase in extracellular potassium as expected. These results show that extracellular potassium modulates Kv7.1 channels and suggests that physiological changes in potassium concentrations may directly control the function of Kv7.1 channels. This may represent a novel regulatory mechanism of excitability and of potassium transport in tissues expressing Kv7.1 channels.
| S-EPMC3175082 | biostudies-other