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.
Projects in the lab include:
The synaptic engram - how networks of cells encode, store and retrieve information
How experience sculpts the brain, using in vivo 2-photon imaging in the visual cortex
The synaptic dysfunction that underlies neurological disorders, including Alzheimer's Disease and autism spectrum disorders
Trafficking of neurotransmitter receptors at synapses
Education History
| 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) |
Selected Publications
- Jason Shepherd, Cameron Day, Elissa Pastuzyn (2018). Compositions and Methods of Use of Arc Capsids. U.S. Patent No. 62/543130. Washington, D.C.:U.S. Patent and Trademark Office.
- Eavri R, Shepherd J, Welsh CA, Flanders GH, Bear MF, Nedivi E (2018). Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging-Related Functional Decline. J Neurosci, 38(39), 8421-8432.
- Wall MJ, Collins DR, Chery SL, Allen ZD, Pastuzyn ED, George AJ, Nikolova VD, Moy SS, Philpot BD, Shepherd JD, Muller J, Ehlers MD, Mabb AM, Correa SAL (2018). The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility. Neuron, 98(6), 1124-1132.e7.
- Shepherd JD (2018). Arc - An endogenous neuronal retrovirus? [Review]. Semin Cell Dev Biol, 77, 73-78.
- Pastuzyn ED, Day CE, Kearns RB, Kyrke-Smith M, Taibi AV, McCormick J, Yoder N, Belnap DM, Erlendsson S, Morado DR, Briggs JAG, Feschotte C, Shepherd JD (2018). The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. Cell, 172(1-2), 275-288.e18.
- Jenks KR, Kim T, Pastuzyn ED, Okuno H, Taibi AV, Bito H, Bear MF, Shepherd JD (2017). Arc restores juvenile plasticity in adult mouse visual cortex. Proc Natl Acad Sci U S A, 114(34), 9182-9187.
- Pastuzyn ED, Shepherd JD (2017). Activity-Dependent Arc Expression and Homeostatic Synaptic Plasticity Are Altered in Neurons from a Mouse Model of Angelman Syndrome. Front Mol Neurosci, 10, 234.
- Day C, Shepherd JD (2015). Arc: building a bridge from viruses to memory. Biochem J, 469(1), e1-3.
- 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.
- Shepherd JD (2012). Memory, plasticity and sleep - A role for calcium permeable AMPA receptors? Front Mol Neurosci, 5, 49.
- 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.
- Shepherd JD, Bear MF (2011). New views of Arc, a master regulator of synaptic plasticity. [Review]. Nat Neurosci, 14(3), 279-84.
- 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.
- 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.
- 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.
- Shepherd JD, Huganir RL (2007). The cell biology of synaptic plasticity: AMPA receptor trafficking. [Review]. Annu Rev Cell Dev Biol, 23, 613-43.
- 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.
- 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.
- 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.
Global Impact
Education History
| Type | School | Degree |
|---|---|---|
| Other Training | Intercultural Exchange in Switzerland, Kantonschule Trogen American Field Scholar (AFS) |
|
| Undergraduate | University of Otago First Class Honours in Neuroscience |
B.S. |
Awards & Honors
| Description | Country |
|---|---|
| Peter and Patricia Gruber International Research Award in Neuroscience | Global |
| International Society for Neurochemistry Young Investigator Award | Global |