scholarly journals Remyelination alters the pattern of myelin in the cerebral cortex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jennifer Orthmann-Murphy ◽  
Cody L Call ◽  
Gian C Molina-Castro ◽  
Yu Chen Hsieh ◽  
Matthew N Rasband ◽  
...  
Keyword(s):  
Time Lapse ◽  
Cognitive Disability ◽  
Cortical Circuits ◽  
Cortical Layers ◽  
Two Photon ◽  
Myelin Sheaths ◽  
Adult Mice ◽  
Cortical Gray Matter ◽  
Circuit Function

Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here, we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.

scholarly journals Remyelination alters the pattern of myelin in the cerebral cortex

2020 ◽  
Author(s):  
Jennifer Orthmann-Murphy ◽  
Cody L. Call ◽  
Gian Carlo Molina-Castro ◽  
Yu Chen Hsieh ◽  
Matthew N. Rasband ◽  
...  
Keyword(s):  
Time Lapse ◽  
Cognitive Disability ◽  
Cortical Circuits ◽  
Cortical Layers ◽  
Two Photon ◽  
Myelin Sheaths ◽  
Adult Mice ◽  
Cortical Gray Matter ◽  
Circuit Function

ABSTRACTDestruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. The repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.

scholarly journals Motor Learning Drives Dynamic Patterns of Intermittent Myelination on Behaviorally-Activated Axons

2021 ◽  
Author(s):  
Clara M. Bacmeister ◽  
Rongchen Huang ◽  
Michael A. Thornton ◽  
Lauren Conant ◽  
Anthony R. Chavez ◽  
...  
Keyword(s):  
Motor Learning ◽  
Computational Modeling ◽  
Learning And Memory ◽  
Neuronal Activity ◽  
Neural Circuits ◽  
Cortical Layers ◽  
Nodes Of Ranvier ◽  
Two Photon ◽  
Myelin Sheaths

Myelin plasticity occurs when newly-formed and pre-existing oligodendrocytes remodel existing myelination. Recent studies show these processes occur in response to changes in neuronal activity and are required for learning and memory. However, the link between behaviorally-relevant neuronal activity and circuit-specific changes in myelination remains unknown. Using longitudinal, in vivo two-photon imaging and targeted labeling of behaviorally-activated neurons, we explore how the pattern of intermittent myelination is altered on individual cortical axons during learning of a dexterous reach task. We show that learning-induced plasticity is targeted to behaviorally-activated axons and occurs in a staged response across cortical layers. During learning, myelin sheaths retract, lengthening nodes of Ranvier. Following learning, addition of new sheaths increases the number of continuous stretches of myelination. Computational modeling suggests these changes initially slow and subsequently increase conduction speed. Thus, behaviorally-activated, circuit-specific changes to myelination may fundamentally alter how information is transferred in neural circuits during learning.

scholarly journals In Vivo Imaging of Cerebral Microvascular Plasticity from Birth to Death

2012 ◽  
Vol 33 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Roa Harb ◽  
Christina Whiteus ◽  
Catarina Freitas ◽  
Jaime Grutzendler
Keyword(s):  
Large Scale ◽  
Time Lapse ◽  
Confocal Imaging ◽  
Adult Brain ◽  
Vessel Formation ◽  
Adult Mice ◽  
Age Related ◽  
Vascular Stability

Cerebral function and viability are critically dependent on efficient delivery of oxygen and glucose through the microvasculature. Here, we studied individual microvessels in the intact brain using high-resolution confocal imaging and long-term time-lapse two-photon microscopy across the lifetime of a mouse. In the first postnatal month, we found large-scale sprouting but to our surprise the majority of sprouts underwent pruning and only a small fraction became perfused capillaries. After the first month, microvessel formation and elimination decreased and the net number of vessels stabilized. Although vascular stability was the hallmark of the adult brain, some vessel formation and elimination continued throughout life. In young adult mice, vessel formation was markedly increased after exposure to hypoxia; however, upon return to normoxia, no vessel elimination was observed, suggesting that new vessels constitute a long-term adaptive response to metabolic challenges. This plasticity was markedly reduced in older adults and aging where hypoxia-induced angiogenesis was absent. Our study describes, for the first time in vivo patterns of cerebral microvascular remodeling throughout life. Disruption of the observed balance between baseline turnover and vascular stability may underlie a variety of developmental and age-related degenerative neurological disorders.

scholarly journals Conditioning sharpens the spatial representation of rewarded stimuli in mouse primary visual cortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Pieter M Goltstein ◽  
Guido T Meijer ◽  
Cyriel MA Pennartz
Keyword(s):  
Visual Space ◽  
Spatial Separation ◽  
Time Lapse ◽  
Optical Signal ◽  
Population Coding ◽  
Cortical Representation ◽  
Population Activity ◽  
Two Photon ◽  
Structure Of Population

Reward is often employed as reinforcement in behavioral paradigms but it is unclear how the visuospatial aspect of a stimulus-reward association affects the cortical representation of visual space. Using a head-fixed paradigm, we conditioned mice to associate the same visual pattern in adjacent retinotopic regions with availability and absence of reward. Time-lapse intrinsic optical signal imaging under anesthesia showed that conditioning increased the spatial separation of mesoscale cortical representations of reward predicting- and non-reward predicting stimuli. Subsequent in vivo two-photon calcium imaging revealed that this improved separation correlated with enhanced population coding for retinotopic location, specifically for the trained orientation and spatially confined to the V1 region where rewarded and non-rewarded stimulus representations bordered. These results are corroborated by conditioning-induced differences in the correlation structure of population activity. Thus, the cortical representation of visual space is sharpened as consequence of associative stimulus-reward learning while the overall retinotopic map remains unaltered.

scholarly journals Distinct features of brain perivascular fibroblasts and mural cells revealed by in vivo two-photon imaging

2021 ◽  
pp. 0271678X2110685
Author(s):  
Stephanie K Bonney ◽  
Liam T Sullivan ◽  
Timothy J Cherry ◽  
Richard Daneman ◽  
Andy Y Shih
Keyword(s):  
Cell Types ◽  
Structural Features ◽  
Main Trunk ◽  
Perivascular Niche ◽  
Two Photon ◽  
Mural Cells ◽  
Adult Mice ◽  
Photon Imaging ◽  
Two Photon Imaging

Perivascular fibroblasts (PVFs) are recognized for their pro-fibrotic role in many central nervous system disorders. Like mural cells, PVFs surround blood vessels and express Pdgfrβ. However, these shared attributes hinder the ability to distinguish PVFs from mural cells. We used in vivo two-photon imaging and transgenic mice with PVF-targeting promoters (Col1a1 or Col1a2) to compare the structure and distribution of PVFs and mural cells in cerebral cortex of healthy, adult mice. We show that PVFs localize to all cortical penetrating arterioles and their offshoots (arteriole-capillary transition zone), as well as the main trunk of only larger ascending venules. However, the capillary zone is devoid of PVF coverage. PVFs display short-range mobility along the vessel wall and exhibit distinct structural features (flattened somata and thin ruffled processes) not seen with smooth muscle cells or pericytes. These findings clarify that PVFs and mural cells are distinct cell types coexisting in a similar perivascular niche.

Microprisms for In Vivo Multilayer Cortical Imaging

2009 ◽  
Vol 102 (2) ◽  
pp. 1310-1314 ◽  
Author(s):  
Thomas H. Chia ◽  
Michael J. Levene
Keyword(s):  
Neuronal Damage ◽  
Cell Damage ◽  
Surrounding Tissue ◽  
Wide Field ◽  
Cortical Layers ◽  
Two Photon ◽  
Simultaneous Imaging ◽  
Cortical Imaging ◽  
Layer V

Cortical slices allow for simultaneous imaging of multiple cortical layers. However, slices lack native physiological inputs and outputs. Although in vivo, two-photon imaging preserves the native context, it is typically limited to a depth of <500 μm. In addition, simultaneous imaging of multiple cortical layers is difficult due to the stratified organization of the cortex. We demonstrate the use of 1-mm microprisms for in vivo, two-photon neocortical imaging. These prisms enable simultaneous imaging of multiple cortical layers, including layer V, at an angle typical of slice preparations. Images were collected from the mouse motor and somatosensory cortex and show a nearly 900-μm-wide field of view. At high-magnification imaging using an objective with 1-mm of coverglass correction, resolution is sufficient to resolve dendritic spines on layer V neurons. Images collected using the microprism are comparable to images collected from a traditional slice preparation. Functional imaging of blood flow at various neocortical depths is also presented, allowing for quantification of red blood cell flux and velocity. H&E staining shows the surrounding tissue remains in its native, stratified organization. Estimation of neuronal damage using propidium iodide and a fluorescent Nissl stain reveals cell damage is limited to <100 μm from the tissue–glass interface. Microprisms are a straightforward tool offering numerous advantages for INTO NEOCORTICAL STISSUE.

In vivo two-photon uncaging of glutamate revealing the structure–function relationships of dendritic spines in the neocortex of adult mice

2011 ◽  
Vol 71 ◽  
pp. e206
Author(s):  
Jun Noguchi ◽  
Akira Nagaoka ◽  
Satoshi Watanabe ◽  
Graham C.R. Ellis-Davies ◽  
Kazuo Kitamura ◽  
...  
Keyword(s):  
Structure Function ◽  
Dendritic Spines ◽  
Two Photon ◽  
Adult Mice

scholarly journals Stringent structural plasticity of dendritic spines revealed by two-photon glutamate uncaging in adult mouse neocortex in vivo

2019 ◽  
Author(s):  
Jun Noguchi ◽  
Akira Nagaoka ◽  
Tatsuya Hayama ◽  
Hasan Ucar ◽  
Sho Yagishita ◽  
...  
Keyword(s):  
Time Course ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Structural Plasticity ◽  
Two Photon ◽  
Low Magnesium ◽  
Adult Mice ◽  
First Time

AbstractTwo-photon uncaging of glutamate is widely utilized to characterize structural plasticity in brain slice preparations in vitro. In this study, we investigated spine plasticity by using, for the first time, glutamate uncaging in the neocortex of adult mice in vivo. Spine enlargement was successfully induced in a smaller fraction of spines in the neocortex (22%) than in young hippocampal slices (95%), even under a low magnesium condition. Once induced, the time course and mean amplitudes of long-term enlargement were the same (81%) as those in vitro. However, low-frequency (1–2 Hz) glutamate uncaging caused spine shrinkage in a similar fraction (34%) of spines as in vitro, but spread to the neighboring spines less frequently than in vitro. Thus, we found that structural plasticity can occur similarly in the adult neocortex in vivo as in the hippocampus in vitro, although it happens stringently in a smaller subset of spines.

scholarly journals Phospholipid Composition of APOE Lipoproteins Affects Microglia Activation in an Isoform-specific Manner

2020 ◽  
Author(s):  
Nicholas Fitz ◽  
KyongNyon Nam ◽  
Cody Wolfe ◽  
Florent Letronne ◽  
Brittany Playso ◽  
...  
Keyword(s):  
Phospholipid Composition ◽  
Time Lapse ◽  
Postmortem Brain ◽  
Two Photon ◽  
Activated State ◽  
Microglial Migration ◽  
Human Apoe3 ◽  
High Level ◽  
Microglial Response

Abstract Apolipoprotein E4 (APOE) is the strongest genetic risk factor for Alzheimer’s disease (AD). Our lipidomic analysis identified a common phospholipid signature with a high level of correlation between APOEε3/3 and APOEε4/4 AD postmortem brain samples and native lipoproteins isolated from astrocyte conditioned media of mice expressing human APOE3 or APOE4. Behavioral testing demonstrated that native E3 lipoproteins were more effective than E4 at ameliorating the harmful effects of Aβ on cognition. We posit that APOE isoform-specific differences in the phospholipid composition of native lipoproteins prompt a differential microglial response. Using time-lapse in vivo two-photon imaging we compared the effect of E3 or E4 infused with Aβ and determined that E3 lipoproteins induced a faster microglial migration towards Aβ. To determine how E3 and E4 lipoproteins affect microglial transcriptome in response to Aβ we performed bulk and single cell RNA-seq of WT and Trem2ko mice. We show that compared to E4, cortical infusion of E3 lipoproteins upregulated a higher proportion of genes associated with an activated immune response accompanied by a downregulation of homeostatic genes. scRNA-seq identified microglia-specific clusters affected by Trem2 deficiency suggesting that lack of Trem2 impairs the transition of microglia from homeostatic to an activated state. Compared to E3, E4-expressing microglia showed a reduced Aβ uptake that was additionally aggravated by Trem2 deficiency. Together, our findings have elucidated unique phenotypic and transcriptional differences in the microglial response to Aβ in the presence of E3 or E4 lipoproteins which could impact AD pathogenesis.

scholarly journals Simultaneous two-photon imaging of action potentials and subthreshold inputs in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuki Bando ◽  
Michael Wenzel ◽  
Rafael Yuste
Keyword(s):  
Action Potentials ◽  
Epileptic Seizures ◽  
Cortical Circuits ◽  
Neuronal Populations ◽  
Two Photon ◽  
Cellular Resolution ◽  
Photon Imaging ◽  
Two Photon Imaging ◽  
Voltage Indicator

AbstractTo better understand the input-output computations of neuronal populations, we developed ArcLight-ST, a genetically-encoded voltage indicator, to specifically measure subthreshold membrane potentials. We combined two-photon imaging of voltage and calcium, and successfully discriminated subthreshold inputs and spikes with cellular resolution in vivo. We demonstrate the utility of the method by mapping epileptic seizures progression through cortical circuits, revealing divergent sub- and suprathreshold dynamics within compartmentalized epileptic micronetworks. Two-photon, two-color imaging of calcium and voltage enables mapping of inputs and outputs in neuronal populations in living animals.

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