Assistant Professor of Neurobiology and Anatomy and
Adjunct Assistant Professor of Biochemistry and of
Ophthalmology & Visual Sciences
B.Sc. (Hons) University of Otago, Dunedin, New Zealand
Ph.D. Johns Hopkins University
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
Memory and learning are fundamental brain functions. The overall focus of my research program is to elucidate the protein machinery that mediates memory encoding and storage in the brain: from protein structure to neural circuits. My lab is a multidisciplinary environment in which we combine both top-down approaches that analyze neuronal circuits in vivo as well as bottom-up approaches of dissecting synaptic function and plasticity at the molecular level. Some unresolved questions my lab aims to address in the future include: Identifying the gene program that transduces experience and learning into long-lasting memories in the brain, what cell biological processes this program regulates in neurons and interrogating these processes in the intact brain, in vivo. Previous work identified the immediate early gene Arc as a critical mediator of synaptic plasticity and memory consolidation. One of the major goals of my lab is to elucidate the cellular and molecular functions of Arc at the synapse.
Ongoing studies use a variety of techniques to understand the role of Arc in memory and synaptic plasticity. These include cryo-EM studies of Arc to in vivo two-photon imaging of live neurons in the intact mouse brain. In collaboration with other labs on campus, we are also developing new molecular imaging methodologies, which include super resolution fluorescent imaging of proteins (with Erik Jorgensen) at nanometer resolution, as well as cannula-based imaging of neurons in deep brain structures in vivo (Rajesh Menon). Our ultimate goal is to interrogate synaptic function during learning and memory encoding at nanometer and millisecond resolution in vivo.
Jenks KR, Kim T, Pastuzyn ED, Okuno H, Taibi AV, Bito H, Bear MF, Shepherd JD. Arc restores juvenile plasticity in adult mouse visual cortex. PNAS, In Press.
Pastuzyn ED, Shepherd JD. Arc-dependent Homeostatic Synaptic Plasticity Is Altered in Angelman Syndrome Model Mice. Frontiers in Molecular Neuroscience, In Press.
- 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 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
- Shepherd JD, Bear MF (2011) New views of Arc, a master regulator of synaptic plasticity. Nature Neuroscience 14(3): 279–284
- 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
- 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
- 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
- Shepherd JD, Huganir RL (2007) The cell biology of synaptic plasticity: AMPA receptor trafficking. Annual Review of Cell and Developmental Biology 23:613-643
- 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
- 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
- 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