scholarly journals Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex

2019 ◽  
Author(s):  
Sachiko Murase ◽  
Daniel E. Winkowski ◽  
Ji Liu ◽  
Patrick O. Kanold ◽  
Elizabeth M. Quinlan
Keyword(s):  
Visual Experience ◽  
Adult Mouse ◽  
Activation Threshold ◽  
Two Photon ◽  
Adult Mice ◽  
History Of ◽  
Proteinase Activation ◽  
Ecm Degradation ◽  
Dark Exposure ◽  
Cortical Synapses

AbstractDark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse V1, which allows recovery from amblyopia. Previously we showed that LRx-induced perisynaptic proteolysis of extracellular substrates by MMP9 mediates the enhanced plasticity in binocular adult mice (Murase et al., 2017). However, it is unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and degradation of ECM in the deprived and non-deprived V1. LRx restricted to the amblyopic eye induces equally robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. This homeostatic reduction of MMP2/9 activation threshold by DE enables the visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.

scholarly journals Homeostatic regulation of perisynaptic matrix metalloproteinase 9 (MMP9) activity in the amblyopic visual cortex

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sachiko Murase ◽  
Dan Winkowski ◽  
Ji Liu ◽  
Patrick O Kanold ◽  
Elizabeth M Quinlan
Keyword(s):  
Visual Cortex ◽  
Adult Mouse ◽  
Two Photon ◽  
Adult Mice ◽  
History Of ◽  
Proteinase Activation ◽  
Ecm Degradation ◽  
Dark Exposure ◽  
Cortical Synapses ◽  
Metalloproteinase 9

Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse primary visual cortex (V1), which allows subsequent recovery from amblyopia. Previously we showed that perisynaptic proteolysis by MMP9 mediates the enhancement of plasticity by LRx in binocular adult mice (Murase et al., 2017). However, it was unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and extracellular matrix (ECM) degradation in deprived and non-deprived V1. Indeed, LRx restricted to the amblyopic eye is sufficient to induce robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. The homeostatic reduction of the MMP2/9 activation threshold by DE enables visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.

scholarly journals Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Sachiko Murase ◽  
Crystal L Lantz ◽  
Elizabeth M Quinlan
Keyword(s):  
Critical Period ◽  
Adult Mouse ◽  
Ocular Dominance ◽  
Visual Deprivation ◽  
Monocular Deprivation ◽  
Genetic Ablation ◽  
Dark Exposure ◽  
Cortical Synapses ◽  
Mouse Visual Cortex ◽  
Metalloproteinase 9

The sensitivity of ocular dominance to regulation by monocular deprivation is the canonical model of plasticity confined to a critical period. However, we have previously shown that visual deprivation through dark exposure (DE) reactivates critical period plasticity in adults. Previous work assumed that the elimination of visual input was sufficient to enhance plasticity in the adult mouse visual cortex. In contrast, here we show that light reintroduction (LRx) after DE is responsible for the reactivation of plasticity. LRx triggers degradation of the ECM, which is blocked by pharmacological inhibition or genetic ablation of matrix metalloproteinase-9 (MMP-9). LRx induces an increase in MMP-9 activity that is perisynaptic and enriched at thalamo-cortical synapses. The reactivation of plasticity by LRx is absent in Mmp9−/− mice, and is rescued by hyaluronidase, an enzyme that degrades core ECM components. Thus, the LRx-induced increase in MMP-9 removes constraints on structural and functional plasticity in the mature cortex.

Oral Infectivity of Vibrio vulnificus in Suckling Mice

1987 ◽  
Vol 50 (12) ◽  
pp. 1013-1016 ◽  
Author(s):  
ANTOLIN L. REYES ◽  
CLIFFORD H. JOHNSON ◽  
PROCTER L. SPAULDING ◽  
GERARD N. STELMA
Keyword(s):  
Adult Mouse ◽  
Vibrio Vulnificus ◽  
Close Correlation ◽  
Oral Route ◽  
Environmental Isolates ◽  
Suckling Mice ◽  
Virulent Isolate ◽  
Adult Mice ◽  
Lethal Doses ◽  
Intraperitoneal Inoculation

Lethal doses of 11 clinical and environmental isolates of Vibrio vulnificus were determined in suckling mice after oral challenge. With one exception, isolates that were virulent to iron-overloaded adult mice after intraperitoneal inoculation were highly lethal to the infant mice (>50% lethality at 105 CFU/mouse). The virulent isolate that failed to kill infant mice at 105 CFU had lost its invasiveness. Conditionally virulent isolates that were virulent only to simultaneously iron-overloaded and immunosuppressed adult mice required > 109 CFU to kill the infant mice. Avirulent isolates failed to kill at >109 CFU/mouse. There were no significant differences in the lethalities of clinical and environmental isolates. These findings demonstrated a close correlation between virulence in the iron-overloaded adult mouse and infectivity by the oral route.

scholarly journals Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus.

1995 ◽  
Vol 15 (2) ◽  
pp. 671-681 ◽  
Author(s):  
A E Sollbach ◽  
G E Wu
Keyword(s):  
Heavy Chain ◽  
Adult Mouse ◽  
Fetal Liver ◽  
Immunoglobulin Heavy Chain ◽  
Antigen Receptors ◽  
Adult Mice ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Fetal Liver Cells

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.

scholarly journals Microvascular Sprouting, Extension, and Creation of New Capillary Connections with Adaptation of the Neighboring Astrocytes in Adult Mouse Cortex under Chronic Hypoxia

2013 ◽  
Vol 34 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Kazuto Masamoto ◽  
Hiroyuki Takuwa ◽  
Chie Seki ◽  
Junko Taniguchi ◽  
Yoshiaki Itoh ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Fluorescent Protein ◽  
Vascular Endothelial Cells ◽  
Three Dimensional ◽  
Vascular Endothelial ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Mouse Cortex ◽  
Hypoxia Adaptation ◽  
Green Fluorescent

The present study aimed to determine the spatiotemporal dynamics of microvascular and astrocytic adaptation during hypoxia-induced cerebral angiogenesis. Adult C57BL/6J and Tie2-green fluorescent protein (GFP) mice with vascular endothelial cells expressing GFP were exposed to normobaric hypoxia for 3 weeks, whereas the three-dimensional microvessels and astrocytes were imaged repeatedly using two-photon microscopy. After 7 to14 days of hypoxia, a vessel sprout appeared from the capillaries with a bump-like head shape (mean diameter 14  μm), and stagnant blood cells were seen inside the sprout. However, no detectable changes in the astrocyte morphology were observed for this early phase of the hypoxia adaptation. More than 50% of the sprouts emerged from capillaries 60  μm away from the center penetrating arteries, which indicates that the capillary distant from the penetrating arteries is a favored site for sprouting. After 14 to 21 days of hypoxia, the sprouting vessels created a new connection with an existing capillary. In this phase, the shape of the new vessel and its blood flow were normalized, and the outside of the vessels were wrapped with numerous processes from the neighboring astrocytes. The findings indicate that hypoxia-induced cerebral angiogenesis provokes the adaptation of neighboring astrocytes, which may stabilize the blood–brain barrier in immature vessels.

scholarly journals A Protracted Sensitive Period Regulates the Development of Cross-Modal Sound–Shape Associations in Humans

2019 ◽  
Vol 30 (10) ◽  
pp. 1473-1482 ◽  
Author(s):  
Suddha Sourav ◽  
Ramesh Kekunnaya ◽  
Idris Shareef ◽  
Seema Banerjee ◽  
Davide Bottari ◽  
...  
Keyword(s):  
Visual Experience ◽  
Sensitive Period ◽  
Congenital Blindness ◽  
Transient Period ◽  
History Of ◽  
Modality Combinations

Humans preferentially match arbitrary words containing higher- and lower-frequency phonemes to angular and smooth shapes, respectively. Here, we investigated the role of visual experience in the development of audiovisual and audiohaptic sound–shape associations (SSAs) using a unique set of five groups: individuals who had suffered a transient period of congenital blindness through congenital bilateral dense cataracts before undergoing cataract-reversal surgeries (CC group), individuals with a history of developmental cataracts (DC group), individuals with congenital permanent blindness (CB group), individuals with late permanent blindness (LB group), and controls with typical sight (TS group). Whereas the TS and LB groups showed highly robust SSAs, the CB, CC, and DC groups did not—in any of the modality combinations tested. These results provide evidence for a protracted sensitive period during which aberrant vision prevents SSA acquisition. Moreover, the finding of a systematic SSA in the LB group demonstrates that representations acquired during the sensitive period are resilient to loss despite dramatically changed experience.

scholarly journals AGE AND SUSCEPTIBILITY OF MICE TO COXSACKIE A VIRUSES

1962 ◽  
Vol 115 (4) ◽  
pp. 745-762 ◽  
Author(s):  
A. Martin Lerner ◽  
Howard S. Levin ◽  
Maxwell Finland
Keyword(s):  
Antibody Formation ◽  
Adult Mouse ◽  
Striated Muscle ◽  
Neutralizing Antibody ◽  
Subclinical Infection ◽  
Pathological Changes ◽  
Adult Mice ◽  
Hind Limbs ◽  
High Yields ◽  
Old Mice

Mice varying in age from 1 day to 8 months were inoculated intraperitoneally with Coxsackie A virus, type 9 and studies were made of the quantity of virus in striated muscle and myocardium, the presence of neutralizing antibody in the serum, and the pathological changes in the tissues. The hind limbs of young (1- to 20-day-old) mice yielded high titers of virus and showed diffuse myositis, whereas only low yields of virus and focal myositis were obtained in older mice. In the 20-day-old mice the skeletal lesions were not accompanied by manifest symptoms and histologically showed evidence of regeneration progressing from the 3rd to the 11th day after inoculation. Older mice showed no symptoms and only focal myositis and low yields of virus were found in their hind limbs. Coxsackie A9 virus replicated to relatively low titers in the hearts of young (1- to 40-day-old) mice without producing any demonstrable lesions whereas frank myocarditis with high yields of virus were demonstrated in mice infected at 8 months of age. The data suggest that at least for the 2 strains used, the adult mouse should be considered susceptible to subclinical infection with Coxsackie A9 virus. Neither subclinical infection, nor antibody formation was demonstrable in young adult mice inoculated with a strain of Coxsackie A4 virus.

NFIX-Mediated Inhibition of Neuroblast Branching Regulates Migration Within the Adult Mouse Ventricular–Subventricular Zone

2018 ◽  
Vol 29 (8) ◽  
pp. 3590-3604 ◽  
Author(s):  
Oressia Zalucki ◽  
Lachlan Harris ◽  
Tracey J Harvey ◽  
Danyon Harkins ◽  
Jocelyn Widagdo ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Subventricular Zone ◽  
Adult Mouse ◽  
Adult Brain ◽  
Granule Cell Layer ◽  
Transcriptional Level ◽  
Olfactory Responses ◽  
Brain Functions ◽  
Neuroblast Migration ◽  
Adult Mice

Abstract Understanding the migration of newborn neurons within the brain presents a major challenge in contemporary biology. Neuronal migration is widespread within the developing brain but is also important within the adult brain. For instance, stem cells within the ventricular–subventricular zone (V-SVZ) and the subgranular zone of dentate gyrus of the adult rodent brain produce neuroblasts that migrate to the olfactory bulb and granule cell layer of the dentate gyrus, respectively, where they regulate key brain functions including innate olfactory responses, learning, and memory. Critically, our understanding of the factors mediating neuroblast migration remains limited. The transcription factor nuclear factor I X (NFIX) has previously been implicated in embryonic cortical development. Here, we employed conditional ablation of Nfix from the adult mouse brain and demonstrated that the removal of this gene from either neural stem and progenitor cells, or neuroblasts, within the V-SVZ culminated in neuroblast migration defects. Mechanistically, we identified aberrant neuroblast branching, due in part to increased expression of the guanylyl cyclase natriuretic peptide receptor 2 (Npr2), as a factor contributing to abnormal migration in Nfix-deficient adult mice. Collectively, these data provide new insights into how neuroblast migration is regulated at a transcriptional level within the adult brain.

An Introduction to Baths in Rome and Methodologies of This Study

2018 ◽  
Author(s):  
Maryl B. Gensheimer
Keyword(s):  
Architectural Design ◽  
Visual Experience ◽  
Daily Life ◽  
Public Spaces ◽  
Fundamental Importance ◽  
Ancient Rome ◽  
Modern History ◽  
History Of ◽  
Multiple Meanings ◽  
Sociopolitical Forces

Given the fundamental importance of baths to daily life in ancient Rome, this chapter introduces the book and concentrates attention on the best preserved of Rome’s imperial thermae, the Baths of Caracalla, in order to unveil the cultural and sociopolitical forces that shaped monumental public spaces and their visual experience. By outlining the Baths’ architectural design and evocative decoration, this chapter foreshadows new insights into the multiple meanings underlying their embellishment and, therefore, the myriad ways in which imperial patronage can be understood. The chapter sets the stage by examining the importance of baths and bathing in ancient Rome generally before delving into the patronage of Rome’s imperial thermae and the Baths of Caracalla more specifically. Special attention is given to tracing the Baths of Caracalla’s ancient design and more modern history of excavation, as well as situating the author’s arguments and aims within recent scholarly contributions.

scholarly journals UPTAKE AND RETENTION OF FIXED CARBON IN ADULT MICE

1951 ◽  
Vol 34 (5) ◽  
pp. 737-759 ◽  
Author(s):  
Donald L. Buchanan ◽  
Keyword(s):  
Experimental Data ◽  
Adult Mouse ◽  
Co2 Concentration ◽  
Total Carbon ◽  
Insoluble Residue ◽  
Fixed Carbon ◽  
Adult Mice ◽  
Accepted Standard ◽  
Mouse Erythrocyte ◽  
Limiting Values

1. Mice were continuously exposed to air containing C14O2. The specific radioactivities of urea carbon, total fecal carbon, and numerous components of tissue carbon were compared as a function of the duration of exposure with the radioactivity of the air CO2. 2. The data indicate that the total CO2 fixed from the air is proportional to its concentration in the air. 3. When the CO2 concentration in the air is normal (0.03 per cent) about 0.34 per cent of the carbon of urea originates from air CO2. A lesser proportion of the non-urea carbon of urine has its origin from air CO2. 4. Only about 0.0054 per cent of the total fecal carbon is derived from air when the CO2 concentration is 0.03 per cent. The constituents, which are extractable with alcohol and water, contain considerably higher proportions of fixed carbon than either the insoluble residue or the ether-extractable material. 5. The rates of uptake at the beginning of the exposure and the rates of loss at the termination of the exposure differed strikingly among the tissues studied. 6. However, the ultimate ratio of fixed air CO2 carbon to total carbon in these tissues seemed to be approaching limiting values which would not vary by more than a factor of 3 from one another. It appears that of the total organic carbon in an adult mouse approximately 0.01 per cent may originate directly from the CO2 of the air when the animal respires in air having a CO2 concentration of 0.03 per cent, and that 1.8 per cent or more of the total carbon may originate from CO2 within the animal. 7. Data are presented which indicate the life span of the mouse erythrocyte to be 49 days. 8. Calculations made on the basis of these experimental data and the accepted standard for permissible radiation in the human would allow mice to be continuously exposed to air containing 31 µc. per c.m. without ever exceeding the accepted permissible level for humans.

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