Michael B. Hoppa

Academic Appointments

Assistant Professor of Biological Sciences
Assistant Professor in the Molecular and Cellular Biology Graduate Program
Assistant Professor in the Program in Experimental and Molecular Medicine
Member of the Institute for Biomolecular Targeting

Everything we see and do is regulated by electrical signals in our nerves and muscles. The focus of my research over the last decade has been to understand how the proteins that generate and transform these electrical signals in cells actually work. Ion channels, which function like tiny pores in the cell membrane, are crucial for sensing and generating electrical signals. My laboratory uses human disease causing mutations in ion channels as a scientific “compass” to direct our inquiries into how ion channels and their molecular partners control cellular activity in neurons. Ion channel research was catalyzed by the invention of glass electrodes to measure electrical signals in cell membranes. However, the average neuron in a human brain sends electrical signals across cables or axons that are only 1/1000th the width of a human hair while also sometimes spanning a meter in length. Progress in the field of neurobiology has been stymied by the fact that the axon is far too small and delicate for measuring ion channel function with electrodes. In principle, these measurements could be achieved with light in the proper setting. Thus, my laboratory at Dartmouth College focuses on devising and refining optical techniques to measure ion channel activity at the nanometer scale within live neurons using genetically-encoded optical indicators. Combining this optical approach with rodent genetics has allowed us to discover and publish novel modulators of synaptic transmission. Our goal is to expand this area of knowledge and potentially identify critical regulators of human disease in synaptic transmission for future therapeutic avenues.measure physiological outputs from neurons using optogenetic indicators in combinations with genetic and biochemical approaches. As such our future projects are trying to determine the following, please contact us for more details:

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1) Determine how distinct regions of the axonal arborization sculpt propagating APs.

2) Determine how AP shape is coupled to neurotransmitter release at presynaptic terminals.  

3) Identify the signaling mechanism(s) that engages adaptive plasticity of the presynaptic waveform.

4) Determine the mechanisms that stabilize and traffic sodium channels within the axon initial segment.

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345 Life Sciences Center
HB 6044
Biological Sciences
B.A. Reed College
D.Phil. University of Oxford

Selected Publications

Perez-Alvarez, A., Fearey, B., Schulze,C.,  O'Toole, R.J.,  Moeyaert, B.,  Mohr, M.A., Arganda-Carreras, I., Yang, W.,  Wiegert, J.S., Schreiter, E.R., Gee, C.E., Hoppa, M.B.,  Oertner, T.G. Freeze-frame imaging of synaptic activity using SynTagMAhttps://www.biorxiv.org/content/10.1101/538041v1

Panzera, L.C., Hoppa, M.B. Genetically Encoded Voltage Indicators Are Illuminating Subcellular Physiology of the Axon.  Front. Cell. Neurosci., 2019 Mar 1;13:52. doi: 10.3389/fncel.2019.00052

Alpizar, S.A., Cho, I.H., Hoppa, M.B. Subcellular control of membrane excitability in the axon. Curr. Opin. Neurobiol., 2019 Aug;57:117-125. doi: 10.1016/j.conb.2019.01.020.

Alpizar, S.A., Baker, A.L., Gulledge, A.T., Hoppa, M.B.  Loss of Neurofascin-186 Disrupts Alignment of AnkyrinG Relative to Its Binding Partners in the Axon Initial Segment. Front. Cell. Neurosci., 2019 January 22. https://doi.org/10.3389/fncel.2019.00001

Cho, I.H., Panzera, L.C, Chin. M., Hoppa, M.B.  Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points. J Neurosci. 2017 Sep 27;37(39):9519-9533. doi: 10.1523/JNEUROSCI.0891-17.2017.

Kyung, J.W., Cho, I.H., Lee, S., Song, W.K., Ryan, T.A., Hoppa, M.B., Kim, S.H.  Adaptor Protein 2(AP-2) complex is essential for functional axogenesis in hippocampal neurons. SciRep. 2017 Jan 31;7:41620. doi: 10.1038/srep41620.

Baumgart, J.P., Zhou, Z.Y., Hara, M., Cook, D.C., Hoppa, M.B., Ryan, T.A., Hemmings, H.C. Jr.  Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling. Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11959-64.doi: 10.1073/pnas.1500525112.

Hoppa, M.B., Gouzer, G,. Armbruster, M., Ryan, T.A.  Control and plasticity of the presynaptic action potential waveform at small CNS nerve terminals. Neuron. 2014 Nov 19;84(4):778-89. doi: 10.1016/j.neuron.2014.09.038

Hoppa, M.B., Lana, B., Margas, W., Dolphin, A.C., Ryan, T.A. α2δ expression setsmpresynaptic calcium channel abundance and release probability. Nature. 2012 May13;486(7401):122-5. doi: 10.1038/nature11033. PubMed PMID: 22678293; PubMed Central PMCID: PMC3376018.

Ariel, P., Hoppa, M.B., Ryan, T.A. (2012)  Intrinsic variability in Pv, RRP size, Ca(2+) channel repertoire, and presynaptic potentiation in individual synaptic boutons. Front Synaptic Neurosci. 2012;4:9.

Hoppa, M.B., Lana, B., Margas, W., Dolphin, A.C., Ryan, T.A. (2012) α2δ expression sets presynaptic calcium channel abundance and release probability. Nature. May 13;486(7401):122-5.

Hoppa, M.B., Jones, E., Karanauskaite, J., Ramracheya, R., Braun, M., Collins, S.C., Zhang, Q., Clark, A., Eliasson, L., Genoud, C., Macdonald, P.E., Monteith, A.G., Barg, S., Galvanovskis, J., Rorsman, P. (2012) Multivesicular exocytosis in rat pancreatic beta cells. Diabetologia. Apr;55(4):1001-12. doi: 10.1007/s00125-011-2400-5

Collins, S.C., Hoppa, M.B., Walker, J.N., Amisten, S., Abdulkhader, F., Bengtsson, M., Fearnside, J., Ramracheya, R., Toye, A.A., Zhang, Q., Clark, A., Gauguier, D., Rorsman, P. (2010) Progression of diet-induced diabetes in C57Bl6J mice involves functional dissociation of Ca2+ channels from secretory vesicles. Diabetes. May;59(5):1192-201.

Hoppa, M.B., Collins, S., Ramracheya, R., Hodson, L., Amisten, S., Zhang, Q., Johnson, P., Ashcroft, F.M., Rorsman, P. (2009) Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca(2+) channels from secretory granules. Cell Metabolism. Dec;10(6):455-65.

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