Anatomy and Neuroscience - Research Publications

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    EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract
    Dottori, M ; Hartley, L ; Galea, M ; Paxinos, G ; Polizzotto, M ; Kilpatrick, T ; Bartlett, PF ; Murphy, M ; Köntgen, F ; Boyd, AW (NATL ACAD SCIENCES, 1998-10-27)
    Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.
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    Impact of COVID-19 Pandemic on Cardiovascular Testing in Asia: The IAEA INCAPS-COVID Study.
    Kudo, T ; Lahey, R ; Hirschfeld, CB ; Williams, MC ; Lu, B ; Alasnag, M ; Bhatia, M ; Henry Bom, H-S ; Dautov, T ; Fazel, R ; Karthikeyan, G ; Keng, FYJ ; Rubinshtein, R ; Better, N ; Cerci, RJ ; Dorbala, S ; Raggi, P ; Shaw, LJ ; Villines, TC ; Vitola, JV ; Choi, AD ; Malkovskiy, E ; Goebel, B ; Cohen, YA ; Randazzo, M ; Pascual, TNB ; Pynda, Y ; Dondi, M ; Paez, D ; Einstein, AJ ; INCAPS COVID Investigators Group, (Elsevier BV, 2021-09)
    BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. OBJECTIVES: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. METHODS: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. RESULTS: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. CONCLUSIONS: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.
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    A method for detecting functional activity related expression in gross brain regions, specific brain nuclei and individual neuronal cell bodies and their projections
    Murphy, M ; Greferath, U ; Wilson, YM (BIOMED CENTRAL LTD, 2007-02-20)
    We have developed a system to visualize functionally activated neurons and their projections in the brain. This system utilizes a transgenic mouse, fos-tau-lacZ (FTL), which expresses the marker gene, lacZ, in neurons and their processes after activation by many different stimuli. This system allows the imaging of activation from the level of the entire brain surface, through to individual neurons and their projections. The use of this system involves detection of neuronal activation by histochemical or immunohistochemical detection of beta-galactosidase (betagal), the product of the lacZ gene. Furthermore, the underlying brain state of the FTL mice determines the basal levels of expression of betagal. Here we describe in detail our protocols for detection of FTL expression in these mice and discuss the main variables which need to be considered in the use of these mice for the detection and mapping of functionally activated neurons, circuits and regions in the brain.
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    Neurons Specifically Activated by Fear Learning in Lateral Amygdala Display Increased Synaptic Strength
    Butler, CW ; Wilson, YM ; Oyrer, J ; Karle, TJ ; Petrou, S ; Gunnersen, JM ; Murphy, M ; Reid, CA (SOC NEUROSCIENCE, 2018)
    The lateral amygdala (LA) plays a critical role in the formation of fear-conditioned associative memories. Previous studies have used c-fos regulated expression to identify a spatially restricted population of neurons within the LA that is specifically activated by fear learning. These neurons are likely to be a part of a memory engram, but, to date, functional evidence for this has been lacking. We show that neurons within a spatially restricted region of the LA had an increase in both the frequency and amplitude of spontaneous postsynaptic currents (sPSC) when compared to neurons recorded from home cage control mice. We then more specifically addressed if this increased synaptic activity was limited to learning-activated neurons. Using a fos-tau-LacZ (FTL) transgenic mouse line, we developed a fluorescence-based method of identifying and recording from neurons activated by fear learning (FTL+ ) in acute brain slices. An increase in frequency and amplitude of sPSCs was observed in FTL+ neurons when compared to nonactivated FTL- neurons in fear-conditioned mice. No learning-induced changes were observed in the action potential (AP) input-output relationships. These findings support the idea that a discrete LA neuron population forms part of a memory engram through changes in synaptic connectivity.
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    Reduction of p75 neurotrophin receptor ameliorates the cognitive deficits in a model of Alzheimer's disease
    Murphy, M ; Wilson, YM ; Vargas, E ; Munro, KM ; Smith, B ; Huang, A ; Li, Q-X ; Xiao, J ; Masters, CL ; Reid, CA ; Barrett, GL (ELSEVIER SCIENCE INC, 2015-02)
    Alzheimer's disease (AD) is an extremely prevalent cause of dementia. It is characterized by progressive memory loss, confusion, and other behavioral and physiological problems. The amyloid-β (Aβ) protein is thought to be involved in the pathogenesis of AD, and there is evidence that Aβ may act through the p75 neurotrophin receptor (p75) to mediate its pathogenic effects. This raises the possibility that reducing levels of p75 could be a treatment for AD by preventing the effects of Aβ. In this study, we have crossed the transgenic AD model mice, Tg2576, with p75(-/-) mice to generate Tg2576/p75(+/-) mice with reduced levels of p75. These mice are rescued from the deficits in learning and memory and hippocampal function which were found in the Tg2576 mice. These findings suggest that reduction of p75 can ameliorate some of the primary symptoms of AD.