Fast Hemodynamic Responses in the Visual Cortex of the Awake Mouse (original) (raw)
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Fast hemodynamic responses in the mouse visual cortex
Hemodynamic responses in mice and other species are typically measured under anesthesia. However, anesthesia could influence their relationship to neural activity. To investigate this relationship, we used optical imaging in mouse primary visual cortex (V1). Hemodynamic responses yielded clear maps of retinotopy in both anesthetized and awake mice. However, during wakefulness, responses were four times larger and twice as fast. These differences held whether we induced anesthesia with urethane or isoflurane and whether awake mice were stationary or running on a treadmill. With electrode recordings, we established that the effects of wakefulness reflect changes in neurovascular coupling, not in neural activity. By activating V1 directly via optogenetics, we replicated the effects of wakefulness in terms of timing but not of amplitude. We conclude that neurovascular coupling depends critically on anesthesia and wakefulness: during wakefulness, neural activity is followed by much stronger and quicker hemodynamic responses.
Local and global contributions to hemodynamic activity in mouse cortex
Imaging techniques such as functional magnetic resonance imaging seek to estimate neural signals in local brain regions through measurements of hemodynamic activity. However, hemodynamic activity is accompanied by large vascular fluctuations of unclear significance. To characterize these fluctuations and their impact on estimates of neural signals, we used optical imaging in visual cortex of awake mice. We found that hemodynamic activity can be expressed as the sum of two components, one local and one global. The local component reflected presumed neural signals driven by visual stimuli in the appropriate retinotopic region. The global component constituted large fluctuations shared by larger cortical regions, which extend beyond visual cortex. These fluctuations varied from trial to trial, but they did not constitute noise; they correlated with pupil diameter, suggesting that they reflect variations in arousal or alertness. Distinguishing local and global contributions to hemodynamic activity may help understand neurovascular coupling and interpret measurements of hemodynamic responses.
Investigating neural–hemodynamic coupling and the hemodynamic response function in the awake rat
NeuroImage, 2006
An understanding of the relationship between changes in neural activity and the accompanying hemodynamic response is crucial for accurate interpretation of functional brain imaging data and in particular the blood oxygen level-dependent (BOLD) fMRI signal. Much physiological research investigating this topic uses anesthetized animal preparations, and yet, the effects of anesthesia upon the neural and hemodynamic responses measured in such studies are not well understood. In this study, we electrically stimulated the whisker pad of both awake and urethane anesthetized rats at frequencies of 1 -40 Hz. Evoked field potential responses were recorded using electrodes implanted into the contralateral barrel cortex. Changes in hemoglobin oxygenation and concentration were measured using optical imaging spectroscopy, and cerebral blood flow changes were measured using laser Doppler flowmetry. A linear neural -hemodynamic coupling relationship was found in the awake but not the anesthetized animal preparation. Over the range of stimulation conditions studied, hemodynamic response magnitude increased monotonically with summed neural activity in awake, but not in anesthetized, animals. Additionally, the temporal structure of the hemodynamic response function was different in awake compared to anesthetized animals. The responses in each case were well approximated by gamma variates, but these were different in terms of mean latency (approximately 2 s awake; 4 s anesthetized) and width (approximately 0.6 s awake; 2.5 s anesthetized). These findings have important implications for research into the intrinsic signals that underpin BOLD fMRI and for biophysical models of cortical hemodynamics and neural -hemodynamic coupling. D
Scientific reports, 2015
Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel 'modular' anesthesia that combined injectable (fentanyl-fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To characterize sensory-evoked cortical hemodynamic responses, we used optical imaging spectroscopy to produce functional maps of changes in tissue oxygenation and blood volume in response to mechanical whisker stimulation. Following fine-tuning of the anesthetic regime, stimulation elicited large and robust hemodynamic responses in the somatosensory cortex, ch...
Brain Research, 2011
The present work evaluated the reproducibility and variance of the cerebral blood flow (CBF) response to natural whisker stimulation in the barrel cortex of awake behaving mice. The animal was placed on an air float ball that allowed the animal to walk, while the head of the animal was fixed in a custom-made stereotactic apparatus. Dynamic CBF changes in the barrel cortex and animal locomotion were simultaneously monitored with laser-Doppler flowmetry (LDF) and an optical motion sensor that detected the rotation distance of the ball, respectively. Whisker stimulation-induced CBF measured under daytime and nighttime conditions showed consistent responses (24% and 23% of the prestimulus baseline, respectively), whereas the amount of locomotion was 1.4 times higher during nighttime relative to daytime. Repeated longitudinal experiments over 7 days showed a reproducible, evoked CBF (13-26% relative to the baseline among 7 animals).
Journal of Cerebral Blood Flow and Metabolism, 2002
Optical imaging spectroscopy was used to measure the hemodynamic response of somatosensory cortex to stimulation of the whiskers. Responses to brief puffs of air were compared in anesthetized and unanesthetized rats. The hemodynamic response was approximately four times larger in the unanesthetized animal than the corresponding anesthetized animal. In unanesthetized animals, a short-latency (approximately 400 milliseconds) short-duration (approximately 300 milliseconds) hemodynamic startle response was observed. General linear model analysis was used to extract this component from the time series, and revealed an underlying short-latency increase in deoxygenated hemoglobin in response to somatosensory stimulation. It is proposed that anesthesia can have a marked affect on the relation between changes in blood volume and blood flow. This work represents a step in the development of an experimental model that can be used to investigate fundamental neurologic processes in the awake-behaving rodent.
Journal of applied physiology (Bethesda, Md. : 1985), 2003
During wakefulness, increases in the partial pressure of arterial CO(2) result in marked rises in cortical blood flow. However, during stage III-IV, non-rapid eye movement (NREM) sleep, and despite a relative state of hypercapnia, cortical blood flow is reduced compared with wakefulness. In the present study, we tested the hypothesis that, in normal subjects, hypercapnic cerebral vascular reactivity is decreased during stage III-IV NREM sleep compared with wakefulness. A 2-MHz pulsed Doppler ultrasound system was used to measure the left middle cerebral artery velocity (MCAV; cm/s) in 12 healthy individuals while awake and during stage III-IV NREM sleep. The end-tidal Pco(2) (Pet(CO(2))) was elevated during the awake and sleep states by regulating the inspired CO(2) load. The cerebral vascular reactivity to CO(2) was calculated from the relationship between Pet(CO(2)) and MCAV by using linear regression. From wakefulness to sleep, the Pet(CO(2)) increased by 3.4 Torr (P < 0.001) ...
Complex spatiotemporal haemodynamic response following sensory stimulation in the awake rat
NeuroImage, 2013
Detailed understanding of the haemodynamic changes that underlie non-invasive neuroimaging techniques such as blood oxygen level dependent functional magnetic resonance imaging is essential if we are to continue to extend the use of these methods for understanding brain function and dysfunction. The use of animal and in particular rodent research models has been central to these endeavours as they allow in-vivo experimental techniques that provide measurements of the haemodynamic response function at high temporal and spatial resolution. A limitation of most of this research is the use of anaesthetic agents which may disrupt or mask important features of neurovascular coupling or the haemodynamic response function. In this study we therefore measured spatiotemporal cortical haemodynamic responses to somatosensory stimulation in awake rats using optical imaging spectroscopy. Trained, restrained animals received non-noxious stimulation of the whisker pad via chronically implanted stimulating microwires whilst optical recordings were made from the contralateral somatosensory cortex through a thin cranial window. The responses we measure from un-anaesthetised animals are substantially different from those reported in previous studies which have used anaesthetised animals. These differences include biphasic response regions (initial increases in blood volume and oxygenation followed by subsequent decreases) as well as oscillations in the response time series of awake animals. These haemodynamic response features do not reflect concomitant changes in the underlying neuronal activity and therefore reflect neurovascular or cerebrovascular processes. These hitherto unreported hyperemic response dynamics may have important implications for the use of anaesthetised animal models for research into the haemodynamic response function.
Vasomotion and neurovascular coupling in the visual thalamus in vivo
2011
Spontaneous contraction and relaxation of arteries (and in some instances venules) has been termed vasomotion and has been observed in an extensive variety of tissues and species. However, its functions and underlying mechanisms are still under discussion. We demonstrate that in vivo spectrophotometry, measured simultaneously with extracellular recordings at the same locations in the visual thalamus of the cat, reveals vasomotion, measured as an oscillation (0.14hz) in the recorded oxyhemoglobin (OxyHb) signal, which appears spontaneously in the microcirculation and can last for periods of hours. During some non-oscillatory periods, maintained sensory stimulation evokes vasomotion lasting ,30s, resembling an adaptive vascular phenomenon. This oscillation in the oxyhaemoblobin signal is sensitive to pharmacological manipulation: it is inducible by chloralose anaesthesia and it can be temporarily blocked by systemic administration of adrenaline or acetylcholine (ACh). During these oscillatory periods, neurovascular coupling (i.e. the relationship between local neural activity and the rate of blood supply to that location) appears significantly altered. This raises important questions with regard to the interpretation of results from studies currently dependent upon a linear relationship between neural activity and blood flow, such as neuroimaging.
Anesthesia and the Quantitative Evaluation of Neurovascular Coupling
Journal of Cerebral Blood Flow & Metabolism, 2012
Anesthesia has broad actions that include changing neuronal excitability, vascular reactivity, and other baseline physiologies and eventually modifies the neurovascular coupling relationship. Here, we review the effects of anesthesia on the spatial propagation, temporal dynamics, and quantitative relationship between the neural and vascular responses to cortical stimulation. Previous studies have shown that the onset latency of evoked cerebral blood flow (CBF) changes is relatively consistent across anesthesia conditions compared with variations in the time-to-peak. This finding indicates that the mechanism of vasodilation onset is less dependent on anesthesia interference, while vasodilation dynamics are subject to this interference. The quantitative coupling relationship is largely influenced by the type and dosage of anesthesia, including the actions on neural processing, vasoactive signal transmission, and vascular reactivity. The effects of anesthesia on the spatial gap between...