Wide-field optical mapping of neural activity in awake mice and the importance of hemodynamic correction

2017 ◽  
Author(s):  
Ying Ma ◽  
David N. Thibodeaux ◽  
Mohammed A. Shaik ◽  
Sharon H. Kim ◽  
Elizabeth M. C. Hillman
Keyword(s):  
Neural Activity ◽  
Optical Mapping ◽  
Wide Field

scholarly journals Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches

2016 ◽  
Vol 371 (1705) ◽  
pp. 20150360 ◽  
Author(s):  
Ying Ma ◽  
Mohammed A. Shaik ◽  
Sharon H. Kim ◽  
Mariel G. Kozberg ◽  
David N. Thibodeaux ◽  
...  
Keyword(s):  
Neural Activity ◽  
High Speed ◽  
Optical Mapping ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
High Sensitivity ◽  
Cellular Level ◽  
Wide Field ◽  
Neural Firing ◽  
Two Photon Microscopy

Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.

scholarly journals Correction to ‘Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches’

2017 ◽  
Vol 372 (1714) ◽  
pp. 20160539 ◽  
Author(s):  
Ying Ma ◽  
Mohammed A. Shaik ◽  
Sharon H. Kim ◽  
Mariel G. Kozberg ◽  
David N. Thibodeaux ◽  
...  
Keyword(s):  
Neural Activity ◽  
Optical Mapping ◽  
Wide Field ◽  
Novel Approaches

scholarly journals Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

2020 ◽  
Author(s):  
Mathew L Rynes ◽  
Daniel Surinach ◽  
Samantha Linn ◽  
Michael Laroque ◽  
Vijay Rajendran ◽  
...  
Keyword(s):  
Neural Activity ◽  
Glutamate Release ◽  
Wide Field ◽  
Dorsal Cortex ◽  
Perceptual Decision Making ◽  
Calcium Activity ◽  
Calcium Indicators ◽  
Stroboscopic Illumination ◽  
Freely Behaving ◽  
Sensory Evoked

ABSTRACTThe advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the “Mesoscope,” a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 µm. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.

scholarly journals A distributed neocortical action map associated with reach-to-grasp

2020 ◽  
Author(s):  
Eros Quarta ◽  
Alessandro Scaglione ◽  
Jessica Lucchesi ◽  
Leonardo Sacconi ◽  
Anna Letizia Allegra Mascaro ◽  
...  
Keyword(s):  
Motor Control ◽  
Neural Activity ◽  
Wide Field ◽  
Activity Levels ◽  
Large Network ◽  
Reach To Grasp ◽  
Neural Repair ◽  
Neocortical Dynamics ◽  
Motor Areas

ABSTRACTReach-to-Grasp (RtG) is known to be dependent upon neocortical circuits and extensive research has provided insights into how selected neocortical areas contribute to control dexterous movements. Surprisingly, little infor-mation is available on the global neocortical computations underlying RtG in the mouse. Here, we characterized, employing fluorescence wide-field cal-cium imaging, the neocortex-wide dynamics from mice engaging in a RtG task. We demonstrate that, beyond canonical motor regions, several areas, such as the visual and the retrosplenial cortices, also increase their activ-ity levels during successful RtGs. Intriguingly, homologous regions across the ipsilateral hemisphere are also involved. Functional connectivity among areas increases transiently from rest to planning, and decreases during move-ment. Two anti-correlated neocortical networks emerged during movement. At variance, neural activity levels scale linearly with kinematics measures of successful RtGs in secondary motor areas. Our findings establish the coex-istence of distributed and localized neocortical dynamics for efficient control of complex movements.SIGNIFICANCE STATEMENTIn mammals, including humans, the cerebral cortex is known to be critical for the correct execution of dexterous movements. Despite the importance of the mouse for elucidating the neural circuitry for motor control, its neocortex-wide dynamics during RtG are largely unexplored. We used in-vivo fluores-cence microscopy to characterize the neural activity across the neocortex as mice performed a reach-to-grasp task. We show that for such complex movements, a large network of neocortical areas gets involved, while movement kinematics correlates with neural activity in secondary motor areas. These findings indicate the coexistence, at the mesoscale level, of distributed and localized neocortical dynamics for the execution of fine movements. This study offers a novel view on the neocortical correlates of motor control, with potential implications for neural repair.

scholarly journals Rapid fluctuations in functional connectivity of cortical networks encode spontaneous behavior

2021 ◽  
Author(s):  
Hadas Benisty ◽  
Andrew H Moberly ◽  
Sweyta Lohani ◽  
Daniel Barson ◽  
Ronald R Coifman ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Neural Activity ◽  
Large Scale ◽  
Analytical Framework ◽  
Network Activity ◽  
Wide Field ◽  
Time Varying ◽  
Cortical Networks ◽  
Novel Approach ◽  
Spontaneous Behavior

Experimental work across a variety of species has demonstrated that spontaneously generated behaviors are robustly coupled to variation in neural activity within the cerebral cortex. Indeed, functional magnetic resonance imaging (fMRI) data suggest that functional connectivity in cortical networks varies across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these studies generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior typically observed in awake animals. Here, we took advantage of recent developments in wide-field, mesoscopic calcium imaging to monitor neural activity across the neocortex of awake mice. Applying a novel approach to quantifying time-varying functional connectivity, we show that spontaneous behaviors are more accurately represented by fast changes in the correlational structure versus the magnitude of large-scale network activity. Moreover, dynamic functional connectivity reveals subnetworks that are not predicted by traditional anatomical atlas-based parcellation of the cortex. These results provide insight into how behavioral information is represented across the mammalian neocortex and demonstrate a new analytical framework for investigating time-varying functional connectivity in neural networks.

scholarly journals Lights, camera, path splitter: a new approach for truly simultaneous dual optical mapping of the heart with a single camera

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Rafael Jaimes ◽  
Damon McCullough ◽  
Bryan Siegel ◽  
Luther Swift ◽  
James Hiebert ◽  
...  
Keyword(s):  
Optical Mapping ◽  
Frame Rate ◽  
Small Rodent ◽  
Wide Field ◽  
Single Camera ◽  
Spatiotemporal Resolution ◽  
Cardiovascular Research ◽  
Excitation Light ◽  
Physiological Models ◽  
Dual Mapping

Abstract Background Optical mapping of transmembrane voltage and intracellular calcium is a powerful tool for investigating cardiac physiology and pathophysiology. However, simultaneous dual mapping of two fluorescent probes remains technically challenging. We introduce a novel, easy-to-use approach that requires a path splitter, single camera and excitation light to simultaneously acquire voltage and calcium signals from whole heart preparations, which can be applied to other physiological models – including neurons and isolated cardiomyocytes. Results Complementary probes were selected that could be excited with a single wavelength light source. Langendorff-perfused hearts (rat, swine) were stained and imaged using a sCMOS camera outfitted with an optical path splitter to simultaneously acquire two emission fields at high spatial and temporal resolution. Voltage (RH237) and calcium (Rhod2) signals were acquired concurrently on a single sensor, resulting in two 384 × 256 images at 814 frames per second. At this frame rate, the signal-to-noise ratio was 47 (RH237) and 85 (Rhod2). Imaging experiments were performed on small rodent hearts, as well as larger pig hearts with sufficient optical signals. In separate experiments, each dye was used independently to assess crosstalk and demonstrate signal specificity. Additionally, the effect of ryanodine on myocardial calcium transients was validated – with no measurable effect on the amplitude of optical action potentials. To demonstrate spatial resolution, ventricular tachycardia was induced –resulting in the novel finding that spatially discordant calcium alternans can be present in different regions of the heart, even when electrical alternans remain concordant. The described system excels in providing a wide field of view and high spatiotemporal resolution for a variety of cardiac preparations. Conclusions We report the first multiparametric mapping system that simultaneously acquires calcium and voltage signals from cardiac preparations, using a path splitter, single camera and excitation light. This approach eliminates the need for multiple cameras, excitation light patterning or frame interleaving. These features can aid in the adoption of dual mapping technology by the broader cardiovascular research community, and decrease the barrier of entry into panoramic heart imaging, as it reduces the number of required cameras.

scholarly journals Decoding of cortex-wide brain activity from local recordings of neural potentials

2021 ◽  
Author(s):  
Xin Liu ◽  
Chi Ren ◽  
Zhisheng Huang ◽  
Madison Wilson ◽  
Jeong-Hoon Kim ◽  
...  
Keyword(s):  
Neural Activity ◽  
Large Scale ◽  
Neural Circuit ◽  
Brain Activity ◽  
Wide Field ◽  
Dorsal Cortex ◽  
Surface Potentials ◽  
Brain Surface ◽  
Neural Activities ◽  
Cortical Regions

Objective. Electrical recordings of neural activity from brain surface have been widely employed in basic neuroscience research and clinical practice for investigations of neural circuit functions, brain-computer interfaces, and treatments for neurological disorders. Traditionally, these surface potentials have been believed to mainly reflect local neural activity. It is not known how informative the locally recorded surface potentials are for the neural activities across multiple cortical regions. Approach. To investigate that, we perform simultaneous local electrical recording and wide-field calcium imaging in awake head-fixed mice. Using a recurrent neural network model, we try to decode the calcium fluorescence activity of multiple cortical regions from local electrical recordings. Main results. The mean activity of different cortical regions could be decoded from locally recorded surface potentials. Also, each frequency band of surface potentials differentially encodes activities from multiple cortical regions so that including all the frequency bands in the decoding model gives the highest decoding performance. Despite the close spacing between recording channels, surface potentials from different channels provide complementary information about the large-scale cortical activity and the decoding performance continues to improve as more channels are included. Finally, we demonstrate the successful decoding of whole dorsal cortex activity at pixel-level using locally recorded surface potentials. Significance. These results show that the locally recorded surface potentials indeed contain rich information of the large-scale neural activities, which could be further demixed to recover the neural activity across individual cortical regions. In the future, our cross-modality inference approach could be adapted to virtually reconstruct cortex-wide brain activity, greatly expanding the spatial reach of surface electrical recordings without increasing invasiveness. Furthermore, it could be used to facilitate imaging neural activity across the whole cortex in freely moving animals, without requirement of head-fixed microscopy configurations.

scholarly journals Lights, Camera, Path Splitter: A New Approach for Truly Simultaneous Dual Optical Mapping of the Heart with a Single Camera

2019 ◽  
Author(s):  
Rafael Jaimes ◽  
Damon McCullough ◽  
Bryan Siegel ◽  
Luther Swift ◽  
James Hiebert ◽  
...  
Keyword(s):  
Optical Mapping ◽  
Frame Rate ◽  
Small Rodent ◽  
Wide Field ◽  
Single Camera ◽  
Spatiotemporal Resolution ◽  
Cardiovascular Research ◽  
Excitation Light ◽  
Physiological Models ◽  
Dual Mapping

ABSTRACTBackgroundOptical mapping of transmembrane voltage and intracellular calcium is a powerful tool for investigating cardiac physiology and pathophysiology. However, simultaneous dual mapping of two fluorescent probes remains technically challenging. We introduce a novel, easy-to-use approach that requires a path splitter, single camera and excitation light to simultaneously acquire voltage and calcium signals from whole heart preparations, which can be applied to other physiological models – including neurons and isolated cardiomyocytes.ResultsComplementary probes were selected that could be excited with a single wavelength light source. Langendorff-perfused hearts (rat, swine) were stained and imaged using a sCMOS camera outfitted with an optical path splitter to simultaneously acquire two emission fields at high spatial and temporal resolution. Voltage (RH237) and calcium (Rhod2) signals were acquired concurrently on a single sensor, resulting in two 384×256 images at 814 frames per second. At this frame rate, the signal-to-noise ratio was 47 (RH237) and 85 (Rhod2). Imaging experiments were performed on small rodent hearts, as well as larger pig hearts with sufficient optical signals. In separate experiments, each dye was used independently to assess crosstalk and demonstrate signal specificity. Additionally, the effect of ryanodine on myocardial calcium transients was validated – with no measurable effect on the amplitude of optical action potentials. To demonstrate spatial resolution, ventricular tachycardia was induced –resulting in the novel finding that spatially discordant calcium alternans can be present in different regions of the heart, even when electrical alternans remain concordant. The described system excels in providing a wide field of view and high spatiotemporal resolution for a variety of cardiac preparations.ConclusionsWe report the first multiparametric mapping system that simultaneously acquires calcium and voltage signals from cardiac preparations, using a path splitter, single camera and excitation light. This approach eliminates the need for multiple cameras, excitation light patterning or frame interleaving. These features can aid in the adoption of dual mapping technology by the broader cardiovascular research community, and decrease the barrier of entry into panoramic heart imaging, as it reduces the number of required cameras.

scholarly journals Twitches, Blinks, and Fidgets: Important Generators of Ongoing Neural Activity

2018 ◽  
Vol 25 (4) ◽  
pp. 298-313 ◽  
Author(s):  
Patrick J. Drew ◽  
Aaron T. Winder ◽  
Qingguang Zhang
Keyword(s):  
Functional Connectivity ◽  
Neural Activity ◽  
Brain Regions ◽  
Wide Field ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Frequency Range ◽  
Sensory Stimuli ◽  
Motor Actions ◽  
The Brain

Animals and humans continuously engage in small, spontaneous motor actions, such as blinking, whisking, and postural adjustments (“fidgeting”). These movements are accompanied by changes in neural activity in sensory and motor regions of the brain. The frequency of these motions varies in time, is affected by sensory stimuli, arousal levels, and pathology. These fidgeting behaviors can be entrained by sensory stimuli. Fidgeting behaviors will cause distributed, bilateral functional activation in the 0.01 to 0.1 Hz frequency range that will show up in functional magnetic resonance imaging and wide-field calcium neuroimaging studies, and will contribute to the observed functional connectivity among brain regions. However, despite the large potential of these behaviors to drive brain-wide activity, these fidget-like behaviors are rarely monitored. We argue that studies of spontaneous and evoked brain dynamics in awake animals and humans should closely monitor these fidgeting behaviors. Differences in these fidgeting behaviors due to arousal or pathology will “contaminate” ongoing neural activity, and lead to apparent differences in functional connectivity. Monitoring and accounting for the brain-wide activations by these behaviors is essential during experiments to differentiate fidget-driven activity from internally driven neural dynamics.

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