Jason Shepherd, PhD

Research Interests

  • Neurodegenerative Diseases
  • Neurosciences
  • Neurodevelopmental Disorders
  • Synaptic Transmission
  • Synaptic Membranes
  • Synaptic Plasticity
  • Learning and Memory
  • Receptor Trafficking
  • Immediate-Early Proteins
  • Endocytosis
  • Autism Spectrum Disorders
  • Angelman Syndrome
  • Fragile X Syndrome
  • Rett Syndrome
  • Alzheimer's Disease

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Biochemistry - Adjunct Assistant Professor, Neurobiology and Anatomy - Assistant Professor, Ophthalmology/Visual Sciences - Adjunct Assistant Professor

Academic Office Information

  • 801-585-6214
  • James LeVoy Sorenson Molecular Biotechnology Building
    Neurobiology and Anatomy
    36 South Wasatch Drive, Room: 4539
    Salt Lake City, UT 84112

Email: jason.shepherd@neuro.utah.edu

Academic Bio

Brains have an amazing ability to learn and store information for long periods, in some cases a lifetime. In particular, the enduring nature of memory remains a mystery, despite intensive study. How does information storage remain stabile for years, despite constant protein modification and turnover? Moreover, disorders of memory and cognition affect millions of people and are generally intractable to treatment. A major challenge in neuroscience is to understand how neuronal networks are modified through experience and how proteins/genes contribute to circuit modification. However, answering these fundamental questions requires many levels of analysis: from molecular interactions to complex cognition. Clearly, a multidisciplinary and collaborative approach is required. The fascinating and challenging aspect of neuroscience is to bridge these gaps of analysis and be able to synthesize work coming from disparate areas of research.My lab is interested in elucidating the fundamental cellular and molecular processes that underlie memory formation. In particular we are interested in the elucidation of the protein machinery at the synapse that governs long-term storage of information, and how basic cell biological processes have been elaborated in neurons for the purpose of modulating synaptic transmission. In addition, we are interested in how these processes go awry in neurological diseases.It has been known since the 1960s that new protein synthesis is required for stabile memory, yet it remains unclear how and why. Moreover, neural circuits are refined during development through activity-dependent gene and protein expression. Similar macromolecular synthesis is essential for long-term forms of synaptic plasticity such as long-term potentiation (LTP) and depression (LTD). Efforts to identify genes that underlie transcription-dependent plasticity have revealed a set of immediate early genes (IEGs) that target to excitatory synapses. Many of these IEGs such as Arc, Narp, Homer and PKM zeta have critical roles in synaptic function and plasticity, and have also been implicated in various neurological disorders. Among brain IEGs identified to date, Arc is the most tightly coupled to behavioral encoding of information in neuronal circuits. Indeed, Arc’s transcription has been used in many labs as a tool to mark neural circuits involved in behavioral paradigms across many species. Mice that lack Arc are profoundly deficient in long-term memory consolidation and in both synaptic and experience-dependent plasticity. Arc expression is exquisitely fined tuned; transcription is rapid and activity-dependent, mRNA is transported to dendrites and protein is locally translated in response to various signaling pathways. Arc protein regulates the AMPA type glutamate receptor at excitatory synapses. Why is Arc so tightly regulated? How does Arc render memories stabile? What is Arc’s precise synaptic function? The uniqueness of Arc is that it allows one to study mechanisms of neural circuit development and refinement at both the synaptic and circuit level, providing insight in how to bridge molecules and behavior.We primarily use the mouse visual cortex to investigate the mechanisms that underlie experience-dependent plasticity because of the ease of manipulating visual experience and because of its well-defined circuitry. The lab utilizes coordinated biochemical, cell biological, electrophysiological and imaging studies in vitro and in vivo, including state of the art techniques such as in vivo two-photon microscopy and chronic electrophysiological recordings in live animals.

Education History

Type School Degree
Postdoctoral Fellowship The Picower Institute for Learning and Memory, Massachusetts Institute of Technology
K99 award
Postdoctoral Fellow
Postdoctoral Fellowship Howard Hughes Medical Institute
The Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Postdoctoral Fellow
Doctoral Training The Johns Hopkins School of Medicine
Medicine
Ph.D.
Graduate Training University of California, Irvine
Neurobiology and Behavior Graduate Program as an Exchange Abroad Scholar (counted towards undergraduate degree)
Undergraduate University of Otago
First Class Honours in Neuroscience
B.S.
Other Training Intercultural Exchange in Switzerland, Kantonschule Trogen
American Field Scholar (AFS)

Global Impact

Education History

Type School Degree Country
Undergraduate University of Otago
First Class Honours in Neuroscience
B.S. New Zealand
Other Training Intercultural Exchange in Switzerland, Kantonschule Trogen
American Field Scholar (AFS)
Switzerland

Selected Publications

Journal Article

  1. Day C, Shepherd JD (2015). Arc: building a bridge from viruses to memory. Biochem J, 469(1), e1-3.
  2. Gee JM, Smith NA, Fernandez FR, Economo MN, Brunert D, Rothermel M, Morris SC, Talbot A, Palumbos S, Ichida JM, Shepherd JD, West PJ, Wachowiak M, Capecchi MR, Wilcox KS, White JA, Tvrdik P (2014). Imaging activity in neurons and glia with a Polr2a-based and cre-dependent GCaMP5G-IRES-tdTomato reporter mouse. Neuron, 83(5), 1058-72.
  3. Shepherd JD (2012). Memory, plasticity and sleep - A role for calcium permeable AMPA receptors? Front Mol Neurosci, 5, 49.
  4. Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF (2011). Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent beta-amyloid generation. Cell, 147(3), 615-28.
  5. McCurry CL, Shepherd JD, Tropea D, Wang KH, Bear MF, Sur M (2010). Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation. Nat Neurosci, 13(4), 450-7.
  6. Smith-Hicks C, Xiao B, Deng R, Ji Y, Zhao X, Shepherd JD, Posern G, Kuhl D, Huganir RL, Ginty DD, Worley PF, Linden DJ (2010). SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells. Nat Neurosci, 13(9), 1082-9.
  7. Park S, Park JM, Kim S, Kim JA, Shepherd JD, Smith-Hicks CL, Chowdhury S, Kaufmann W, Kuhl D, Ryazanov AG, Huganir RL, Linden DJ, Worley PF (2008). Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron, 59(1), 70-83.
  8. Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF (2006). Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron, 52(3), 445-59.
  9. Shepherd JD, Rumbaugh G, Wu J, Chowdhury S, Plath N, Kuhl D, Huganir RL, Worley PF (2006). Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron, 52(3), 475-84.
  10. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003). Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron, 39(3), 409-21.

Review

  1. Shepherd JD, Bear MF (2011). New views of Arc, a master regulator of synaptic plasticity. [Review]. Nat Neurosci, 14(3), 279-84.
  2. Shepherd JD, Huganir RL (2007). The cell biology of synaptic plasticity: AMPA receptor trafficking. [Review]. Annu Rev Cell Dev Biol, 23, 613-43.

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