scholarly journals Cellular resolution imaging of vestibular processing across the larval zebrafish brain

2018 ◽  
Author(s):  
Itia A. Favre-Bulle ◽  
Gilles Vanwalleghem ◽  
Michael A. Taylor ◽  
Halina Rubinsztein-Dunlop ◽  
Ethan K. Scott

SummaryThe vestibular system, which reports on motion and gravity, is essential to postural control, balance, and egocentric representations of movement and space. The motion needed to stimulate the vestibular system complicates studying its circuitry, so we previously developed a method for fictive vestibular stimulation in zebrafish, using optical trapping to apply physical forces to the otoliths. Here, we combine this fictive stimulation with whole-brain calcium imaging at cellular resolution, delivering a comprehensive map of the brain regions and cellular responses involved in basic vestibular processing. We find these responses to be broadly distributed across the brain, with unique profiles of cellular responses and topography in each brain region. The most widespread and abundant responses involve excitation that is rate coded to the stimulus strength. Other responses, localized to the telencephalon and habenulae, show excitation that is only weakly rate coded and that is sensitive to weak stimuli. Finally, numerous brain regions contain neurons that are inhibited by vestibular stimuli, and these inhibited neurons are often tightly localised spatially within their regions. By exerting separate control over the left and right otoliths, we explore the laterality of brain-wide vestibular processing, distinguishing between neurons with unilateral and bilateral vestibular sensitivity, and revealing patterns by which conflicting vestibular signals from the two ears can be mutually cancelling. Our results show a broader and more extensive network of vestibular responsive neurons than has previously been described in larval zebrafish, and provides a framework for more targeted studies of the underlying functional circuits.

Author(s):  
Gilles Vanwalleghem ◽  
Kevin Schuster ◽  
Michael A. Taylor ◽  
Itia A. Favre-Bulle ◽  
Ethan K. Scott

AbstractInformation about water flow, detected by lateral line organs, is critical to the behavior and survival of fish and amphibians. While certain specific aspects of water flow processing have been revealed through electrophysiology, we lack a comprehensive description of the neurons that respond to water flow and the network that they form. Here, we use brain-wide calcium imaging in combination with microfluidic stimulation to map out, at cellular resolution, all neurons involved in perceiving and processing water flow information in larval zebrafish. We find a diverse array of neurons responding to forward flow, reverse flow, or both. Early in this pathway, in the lateral line ganglia, these are almost exclusively neurons responding to the simple presence of forward or reverse flow, but later processing includes neurons responding specifically to flow onset, representing the accumulated volume of flow during a stimulus, or encoding the speed of the flow. The neurons reporting on these more nuanced details are located across numerous brain regions, including some not previously implicated in water flow processing. A graph theory-based analysis of the brain-wide water flow network shows that a majority of this processing is dedicated to forward flow detection, and this is reinforced by our finding that details like flow velocity and the total volume of accumulated flow are only encoded for the simulated forward direction. The results represent the first brain-wide description of processing for this important modality, and provide a departure point for more detailed studies of the flow of information through this network.Significance statementIn aquatic animals, the lateral line is important for detecting water flow stimuli, but the brain networks that interpret this information remain mysterious. Here, we have imaged the activity of individual neurons across the entire brains of larval zebrafish, revealing all response types and their brain locations as water flow processing occurs. We find some neurons that respond to the simple presence of water flow, and others that are attuned to the flow’s direction, speed, duration, or the accumulated volume of water that has passed during the stimulus. With this information, we modeled the underlying network, describing a system that is nuanced in its processing of water flow simulating forward motion but rudimentary in processing flow in the reverse direction.


2012 ◽  
Vol 25 (0) ◽  
pp. 206
Author(s):  
Michael Barnett-Cowan

Multisensory stimuli originating from the same event can be perceived asynchronously due to differential physical and neural delays. The transduction of and physiological responses to vestibular stimulation are extremely fast, suggesting that other stimuli need to be presented prior to vestibular stimulation in order to be perceived as simultaneous. There is, however, a recent and growing body of evidence which indicates that the perceived onset of vestibular stimulation is slow compared to the other senses, such that vestibular stimuli need to be presented prior to other sensory stimuli in order to be perceived synchronously. Following a review of this literature I will argue that this perceived latency of vestibular stimulation likely reflects the fact that vestibular stimulation is most often associated with sensory events that occur following head movement, that the vestibular system rarely works alone, and that the brain prioritizes physiological response to vestibular stimulation over perceptual awareness of stimulation onset.


2018 ◽  
Vol 28 (23) ◽  
pp. 3711-3722.e3 ◽  
Author(s):  
Itia A. Favre-Bulle ◽  
Gilles Vanwalleghem ◽  
Michael A. Taylor ◽  
Halina Rubinsztein-Dunlop ◽  
Ethan K. Scott

2021 ◽  
Author(s):  
D.P. Leman ◽  
I.A. Chen ◽  
K.A. Bolding ◽  
J. Tai ◽  
L.K. Wilmerding ◽  
...  

AbstractMiniaturized microscopes for head-mounted fluorescence imaging are powerful tools for visualizing neural activity during naturalistic behaviors, but the restricted field of view of first-generation ‘miniscopes’ limits the size of neural populations accessible for imaging. Here we describe a novel miniaturized mesoscope offering cellular-resolution imaging over areas spanning several millimeters in freely moving mice. This system enables comprehensive visualization of activity across entire brain regions or interactions across areas.


2017 ◽  
Author(s):  
Shay Ohayon ◽  
Antonio M. Caravaca-Aguirre ◽  
Rafael Piestun ◽  
James J. DiCarlo

AbstractA major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well-defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive (surface) multiphoton approaches1,2 for deep (>2mm) structures, while Gradient Refreactive Index (GRIN) endoscopes2–4 are thick and cause significant damage upon insertion. Here, we demonstrate a novel microendoscope to image neural activity at arbitrary depths via an ultrathin multimode optical fiber (MMF) probe that is 5-10X thinner than commercially available microendoscopes. We demonstrate micron-scale resolution, multispectral and volumetric imaging. In contrast to previous approaches1,5–8 we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator. Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.


2020 ◽  
Vol 21 ◽  
Author(s):  
Sayed Md Mumtaz ◽  
Gautam Bhardwaj ◽  
Shikha Goswami ◽  
Rajiv Kumar Tonk ◽  
Ramesh K. Goyal ◽  
...  

: The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhort tumor of star-shaped glial cell in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorder like neurofibromatosis and schwanomatosis which develop the tumor in the nervous system. The management of GBM with chemo-radio therapy leads to resistance and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind failure of drugs are due to DNA alkylation in cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bio-active compounds from plants known as phytochemicals, serve as vital sources for anti-cancer drugs. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, podophyllotoxin analogs, camptothecin, curcumin, aloe emodin, quercetin, berberine e.t.c. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancers. However the challenges posed by the presence of BBB/BBTB to restrict passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review we integrated nanotech as novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.


2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.


Author(s):  
Antonina Kouli ◽  
Marta Camacho ◽  
Kieren Allinson ◽  
Caroline H. Williams-Gray

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.


Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.


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