As shown in Figure 4 from Bearer, "Short and long term effects of cocaine on the brain" 1R01DA055184-01A1. Cumulative activity mapped in the brain of a normally behaving mouse over 24 hours shows signal in the olfactory bulb, hippocampus, amygdala, nucleus accumbens, ventral tegmental area and regions of the cerebellum (n = 12, T=5.7, p = 0.01 to 0.001 FDR; blue, low; red, high).
Wild type mice after a naturalistic fearful experience, such as predator stress, display altered projections from the medial prefrontal cortex (mPFC) as traced by manganese-enhanced MRI (MEMRI). Projections from mPFC without a fear experience (blue) go to dorsal raphe (DR and other raphe nuclei and basolateral amygdala (BLA) and shift to other regions after a fear experience (red), periaquaductal gray (PAG) and hypothalamus. Images collected at 24h post Mn(II) injection into mPFC were skull-stripped, normalized and aligned and then statistical parametric mapping (SPM) was performed. Slices from 3D maps (n=24, p < 0.01 FDR, blue, no stress; red, 3 weeks after stress) are overlaid onto a gray scale MR anatomical image. Higher magnification shown in right panels. As shown in Figure 8 from Bearer, "Short and long term effects of cocaine on the brain" 1R01DA055184-01A1.
Elaine Bearer's interest in the brain, the mind, and their disorders propelled her into biomedical sciences. She uses many different imaging technologies, coupled with molecular genetics and computational modeling, to study circuitry dynamics in health and in disease states. Bearer is the recipient of Distinguished Alumni awards from both of her alma maters, Manhattan School of Music (2019) and University of California, San Francisco (2020). She received an honorary professorship from the Strømstad Academy in Sweden (2021). She is an elected fellow of AAAS and of the College of American Pathologists.
Bearer’s research began with discovery of the finest details of membrane dynamics in synaptic transmitter release. She developed imaging labels for anionic lipids and made the earliest observations of membrane lipid rafts. Later, as a Swiss National Science Foundation post-doctoral fellow at Centre Medicale Universitaire with Lelio Orci, she developed quick-freeze deep-etch electron-microscopy to define the structure of endothelial fenestral diaphragms, the gateway between tissue and blood. Bearer's protein biochemistry with Bruce M. Alberts at UCSF seeking actin filament modulators that regulate membrane dynamics identified 110 proteins driving filament formation from human blood platelets.
After moving from UCSF to Brown University and founding her own laboratory, Bearer mapped the gene for one of these newly discovered proteins, kaptin/2E4, on human chromosome 19, for which she contributed the human and mouse sequences. These discoveries showed that mutations in a promoter region lead to inherited diseases, in this case adult-onset deafness (DFNA4). Working in the summer at Marine Biological Laboratory in Woods Hole, MA, Bearer deployed herpes simplex virus as a tool and squid giant axon as an experimental model to discover that amyloid precursor protein (APP), the major component in Alzheimer’s plaques, recruited cytoskeletal motors to intracellular cargo for transport. These studies in endogenous axonal transport mechanics underlie her work tracing brain-wide neuronal projections with MRI.
In 2004, as a Moore Distinguished Scholar on sabbatical from Brown to California Institute of Technology, Bearer worked with physical chemist, Russell E. Jacobs, to pioneer manganese-enhanced magnetic resonance imaging to witness neuronal projections and activity over time in living mouse models for human neuropsychiatric disorders.
Most recently, using this emerging imaging technique together with behavioral paradigms and transgenic animals, the Bearer lab discovered and reported the effect of naturalistic fear on brain-wide neural activity and how activity patterns transition to anxiety-states over time. Now the Bearer team is exploring how early life adversity renders the brain vulnerable to mental and substance use disorders, and how experiences alter forebrain connectivity.
Bearer is a composer of serious music who ponders on implications of her scientific findings on how music evokes emotion.
https://en.wikipedia.org/wiki/Elaine_Bearer
Manhattan School of Music Distinguished Alumni Award (May 2019)
Strømstad Academy, The Neuroscience of Emotion from a Musical Perspective
Neuropathologist Combines Music Composition With Brain Research Listen on KUNM
Uselman, Medina, Gray, Jacobs and Bearer. This comprehensive review of MEMRI presents: the chemical and physical properties of Mn (II); considerations for safe dosing; perspectives on scanning parameters; discussions of biological mechanisms of projection and neural activity mapping; contributions yielded by MEMRI; procedures for image processing; strategies for computational analysis; and concludes with remarks for future directions. This paper provides a resource to guide investigators when applying MEMRI to critical neurobiological problems.-enhanced_magnetic_resonance_imaging_of_neural_projections_and_activity
Longitudinal MEMRI allows imaging of brain-wide activity as it evolves; Brain-wide activity transitions from fear to anxiety, corresponding to behavior; Statistical parametric mapping (SPM) and aligning maps to our new InVivo atlas allows segment-wise quantification of activated voxels across experiential time line, before and at successive time points after naturalistic fear. Transitions from a basal pattern to a fear-provoked pattern to an anxiety-like pattern are reported and their biological mechanisms investigated; A dynamic balance of activity throughout the brain differs in fear - v.s. anxiety-states.
"Evolution of brain-wide activity in the awake behaving mouse after acute fear by longitudinal manganese-enhanced MRI." Uselman, Barto, Jacobs and Bearer. Neuroimage https://doi.org/10.1016/j.neuroimage.2020.116975
Following on discovering the role of APP in axonal transport, the Bearer team went on to determine the effect of dominant mutations in APP on transport using MEMRI. These studies reveal a combined effect of aging and mutant APP expression, with most severe defects in aging mutants, and milder, hard to detect, transport defects in young (6 month-old) mice, just as the human condition predicts. Using a double transgenic that allowed conditional expression of a Swedish-Indiana mutated APP transgenic, Bearer's group showed that transport could be affected within two weeks of turning on or off expression. Future work looks at the combined roles of herpesvirus load and QTL in autophagic genes on cognitive impairment and Alzheimer's pathology using post-mortem samples from Alzheimer's Brain Banks.
In addition, Bearer has a long-standing collaboration with a team of neurosurgeons, chemical engineers and computational biologists to develop methods for modeling biological processes of glioblastoma using the first principles of physics with values based on neuropathological specimens. Utilizing archival pathological material, Bearer, Frieboes and Cristini have pioneered a series of mathematical models describing tumor behavior and predicting treatment outcomes from standard diagnostic tests. Bearer accepts consults.
Bearer also participates in a medical outreach clinic in Guatemala and holds secondary appointments in Neurosurgery and in the UNM Music Department. She teaches medical students and graduate courses and serves on steering and curriculum committees. She teaches musical composition in the Music Department at UNM.
Bearer began composing at age 6, with a performance of some of her compositions in student recitals at the age of 9. During school years, she first studied violin and piano. She then moved to viola and French horn, played in the local community orchestras, and studied with performance faculty at Juilliard School in Manhattan. Still in her teens, Bearer traveled to France to study with Nadia Boulanger, first at Fontainebleau and then in Paris. She obtained a Bachelor’s of Music from The Manhattan School in Theory and Composition, and then a Master’s of Art in Musicology from NYU. Afterward, she left New York for San Francisco for a tenure-track assistant professorship in Music at Lone Mountain College. Her compositions are performed in internationally in Sweden, Norway, Paris, and Geneva, as well as in the USA , locally in Albuquerque and Santa Fe, NM; Providence, RI; New York; New Jersey; San Francisco and Los Angeles, California, as well as many other venues.
Charged with a great curiosity about how music impacts the brain, Bearer embarked on an odyssey in the realm of neuroscience, beginning at Stanford University in human biology with Don Kennedy. In one year, Bearer became Kennedy’s teaching assistant while continuing to teach at San Francisco Conservatory. She then joined John Nicholl’s neurobiology laboratory at Stanford Medical Center, where she made lasting friendships and learned electrophysiology. Deciding that a PhD in neuroscience would be too narrow, she applied and was accepted to the newly founded MD-PhD medical scientist training program at the University of California, San Francisco. More information about her successful and productive scientific career can be found in the BioMedical Science CV posted on her UNM Pathology Faculty website.
Despite the rigors and intensity of a combined MD-PhD career, Bearer continues to compose. A full listing of her compositions is posted in her separate Music CV. While at Brown University from 1991-2001, she held a secondary appointment in the Music Department teaching composition and now holds a secondary appointment in the Music Department at UNM, where she may accept one student per year to study composition.
Bearer's research into the biological basis of brain and neurological diseases is coupled with her deep abiding interest in the mind. She is frequently invited to give public lectures on Music-Mind, some of which can be found on websites such as Vimeo and YouTube. Bearer’s music is serious with historical perspective and novel use of sound and space. Her collaborations with the choreographer, Colleen Cavanaugh, are charged with electronically engineered sounds, while her Magdalene Passion for voices and orchestra is entirely acoustic. Tiger, composed for the Pasadena ProMusica performance in the Science and Art Festival, includes live interactive light projections engineered by John Carpenter, a Los Angeles-based video artist and architect. Her most recent string quartet was performed in Sweden in fall 2021.
Bearer taught for 18 years in the medical school and graduate programs at Brown University. In the Warren Alpert Medical School of Brown University, she was course director for semester-long courses in Systemic Pathology for which she was awarded a number of Dean’s awards for Excellence in Medical Teaching, as well as lecturer for other medical school courses. She has hosted over 70 undergraduates, graduates, and post-doctoral trainees in her lab, some of whom now have their own faculty appointments elsewhere. Her commitment to education is exemplified in service on numerous education committees, both locally and nationally, and chair of the Education Committee for the national American Society for Investigative Pathology elected secretary for the Undergraduate Medical Educators Section of the Association of Pathology Chairs. At Brown she served on the Medical Curriculum Committee, participating in two rounds of curriculum reform towards competencies and integration. She has also served as an elected member of the Medical Curriculum Committee at UNM, as well as a member of steering committees for the graduate program and the MD-PhD program.
Elaine L. Bearer, MD, PhD
Harvey Family Professor and Vice Chair for Research
Department of Pathology
UNM School of Medicine
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