Jason Shepherd

Assistant Professor of Neurobiology and Anatomy and
Adjunct Assistant Professor of Biochemistry and of
Ophthalmology & Visual Sciences

Shepherd

B.Sc. (Hons) University of Otago, Dunedin, New Zealand

Ph.D. Johns Hopkins University

Research

References

jason.shepherd@neuro.utah.edu

Jason Shepherd's Lab Page

Jason Shepherd's PubMed Literature Search

 

Molecular Biology Program

Biological Chemistry Program

Synaptic plasticity, memory and neurological disorders, Memory Formation

Research

Brains have an amazing ability to learn and store information for long periods - in some cases, a lifetime. A major challenge in neuroscience is to understand how neuronal networks are sculpted by experience and how proteins/genes contribute to circuit modification. The goal of our research is to understand information storage, from the molecular level through in vivo neuronal networks and how these processes go awry in neurological disorders. My lab utilizes coordinated biochemical, cell biological, electrophysiological and imaging studies both in vitro and in vivo.
 
We recently discovered a novel mechanism of neuronal communication that resembles the life-cycle of retroviruses (https://www.sciencedirect.com/science/article/pii/S0092867417315040) . The neuronal gene Arc, a master regulator of synaptic plasticity and memory, contains a Gag retroviral homology domain that has conserved secondary structure with HIV-1 that is derived from a distinct family of retrotransposons. Arc protein self-assembles into viral-like capsids that are released from cells and carry RNA/proteins to neighboring cells. Our findings open up a new area of investigation in the cell biology of cell-to-cell communication, by revealing that some retrotransposon-derived genes retain the ability to form capsids that shuttle RNAs and proteins between cells. Ongoing projects in the lab aim to dissect this new intercellular pathway that intersects diverse fields of biology that include virology, extracellular communication, evolutionary biology, gene delivery and neuroscience.
 
Other projects in the lab include:
 
  1. The synaptic engram - how networks of cells encode, store and retrieve information
  2. How experience sculpts the brain, using in vivo 2-photon imaging in the visual cortex
  3. The synaptic dysfunction that underlies neurological disorders, including Alzheimer's Disease and autism spectrum disorders
  4. Trafficking of neurotransmitter receptors at synapses

References

  1. Wall M.J., Collins D.R., Chery S.L., Allen Z.D., Pastuzyn E.D., Nikolova V.D., Moy S.S., Philpot B.D.,Shepherd J.D., Müller J., Ehlers M.D., Mabb A.M., Corrêa S.A.L. The temporal dynamics of Arc expression regulates cognitive flexibility.  Neuron, 2018 May 24. pii: S0896-6273(18)30384-2
  2. Shepherd J.D. Arc - An endogenous neuronal retrovirus? Seminars in Cell & Developmental Biology. 2018 May;77:73-78. doi: 10.1016/j.semcdb.2017.09.029. Epub 2017 Sep 24.
  3. Pastuzyn E.D., Day C.E., Kearns R.B., Kyrke-Smith M., Taibi A.V., McCormick J., Belnap D.M., Yoder N., Erlendsson S., Morado D.R., Briggs J.A.G., Feschotte C. and Shepherd J.D. The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. Cell, 2018 Jan 11;172(1-2):275-288.e18.
  4. Jenks K.R., Kim T., Pastuzyn E.D., Okuno H., Taibi A.V., Bito H., Bear M.F., Shepherd J.D. Arc restores juvenile plasticity in adult mouse visual cortex. PNAS, 2017 Aug 22;114(34):9182-9187.

  5. Pastuzyn E.D. and Shepherd J.D. Arc-dependent Homeostatic Synaptic Plasticity Is Altered in Angelman Syndrome Model Mice. Frontiers in Molecular Neuroscience, 2017 Jul 28;10:234.

  6. Kim G., Nagarajan N., Pastuzyn E.D., Jenks K.R., Capecchi M., Shepherd J.D., Menon R. Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy. Sci Rep. 2017 Mar 20;7:44791. doi: 10.1038/srep44791.

  7. Day C, Shepherd JD (2015) Arc: building a bridge from viruses to memory. Biochem J 469(1):e1-3
  8. 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
  9. Shepherd JD (2012) Memory, plasticity and sleep - A role for calcium permeable AMPA receptors? Front Mol Neurosci 5:49
  10. Wu J, Petralia RS, Kurushima H, Patel H, Jung M, 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 B-Amyloid Generation. Cell 147(3):615-628
  11. Shepherd JD, Bear MF (2011) New views of Arc, a master regulator of synaptic plasticity. Nature Neuroscience 14(3): 279–284
  12. 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 the late phase of LTD in cultured cerebellar purkinje cells. Nature Neuroscience 13(9):1082-9
  13. McCurry C*, Shepherd JD*, Tropea D, Wang K, Bear MF, Sur M (2010) Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation. Nature Neuroscience 13(4):450-7
  14. 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) Eukaryotic elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc essential for mGluR-LTD. Neuron 59(1):70-83
  15. Shepherd JD, Huganir RL (2007) The cell biology of synaptic plasticity: AMPA receptor trafficking. Annual Review of Cell and Developmental Biology 23:613-643
  16. Shepherd JD*, Rumbaugh G*, Wu J, Chowdhury S, Plath N, Kuhl D, Huganir RL, Worley PF (2006) Arc/Arg3.1 Mediates synaptic scaling of AMPA receptors. Neuron 52(3):475-84
  17. Chowdhury S*, Shepherd JD*, Ojuno H, Lyford G, Petralia R, 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
  18. 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

*denotes co-authorship

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Last Updated: 10/4/18