Research Summary

We aim to understand how the brain accomplishes memory. To do this, we combine cutting-edge experimental neuroscience, big data analysis, and computational modeling. We use this multidisciplinary approach to study memory in the brain across many different levels: molecules, neurons, neural circuits, and behaviour. With this combination, we aim to generate a comprehensive understanding of the neurobiological rules of memory in health, disorder, and disease. Such an understanding will guide treatment and prevention of debilitating memory conditions like post-traumatic stress disorder.

Understanding the mechanisms of memory in the brain has immense importance for basic neuroscience and clinical applications. Many different methodologies can be taken to study memory in the brain, which span molecular, cellular, circuit, and behavioural scales. Using a multidisciplinary approach in the mouse, we seek to elucidate the mechanisms of memory across all of these scales. Experimentally, we perform cutting-edge techniques that enable us to identify and manipulate specific molecules, cells, and circuits in the brain (e.g., next-generation RNA sequencing, CRISPR-Cas9, immunohistochemistry, in situ hybridization, viral circuit mapping, chemogenetics, pharmacology). To help interpret and guide our experiments, we also perform big data analysis and computational modeling. We seek to integrate the results of these techniques to comprehensively understand the mechanisms of memory, to benefit both science and society.

Projects

Identifying and disrupting the mechanisms of fear memory in the brain: Fear memory, like that occurring in post-traumatic stress disorder, imposes pronounced health and financial burdens. Our laboratory seeks to identify the precise neurons and genes that mediate fear memory, and to leverage these results to therapeutically disrupt fear memory formation. In this work, we identify critical molecular and cellular targets and examine the effects of both precise (e.g., cell-type-specific Crispr-Cas9) and systemic (e.g., in vivo pharmacologic) disruptions. We aim for this research to provide insight into the causal neurobiological substrates of fear memory, and how these substrates can be perturbed for potential clinical translation.

 

Pursuing distinct streams of memory-associated information in the brain. In recent work (e.g., Cembrowski et al., Cell, 2018), we identified that there are precise features that delineate different subtypes of subiculum projection neurons, with these subtypes varying in both afferent and efferent connectivity as well as working memory contributions. Such a subtype-specific organization may be found in other upstream and downstream regions, which may ultimately underpin brain-wide dissociable streams of cognitive information. By studying these other brain regions in relation to the subiculum, we seek to understand whether there are parallel memory streams that traverse the brain. 

Collaborations

Annie Vogel Ciernia, Dept. of Biochemistry and Molecular Biology and Centre for Brain Health, UBC: gene expression and associated mechanisms in health and disease.

Jesse Jackson, Dept. of Physiology, University of Alberta: cell-type-specific identification and interpretation of claustrum projections.

Maria Ioannou, Dept. of Physiology, University of Alberta: heterogeneity within astrocytes of the hippocampus.

Nelson Spruston, Janelia Research Campus, Howard Hughes Medical Institute: organizational rules of heterogeneity within hippocampal principal neuron classes.

Erik Bloss, Janelia Research Campus, Howard Hughes Medical Institute: anatomical mapping and computational modeling of specific microcircuits in the hippocampus.

Bio

Mark Cembrowski is an Assistant Professor in the Department of Cellular and Physiological Sciences, as well as an Investigator in the Djavad Mowafaghian Centre for Brain Health, at the University of British Columbia. Dr. Cembrowski’s laboratory examines how molecular, cellular, and circuit properties of the brain transform to mediate memory and behaviour. Dr. Cembrowski is also a Visiting Scientist at the Janelia Research Campus of the Howard Hughes Medical Institute and a Next Generation Leader at the Allen Institute.

 

Previously, Mark was a postdoctoral researcher in the Spruston Laboratory at the Janelia Research Campus of the Howard Hughes Medical Institute. In his postdoctoral work, Mark combined experimental and computational approaches to examine the extent of heterogeneity within classical cell types of the hippocampus. This work revealed that all classical cell types exhibit extensive within-cell-type variability, which can ultimately mediate structurally and functionally dissociable streams of hippocampal output. As a graduate student, Mark received his MS and PhD in Applied Mathematics from Northwestern University as a joint student between William Kath, Hermann Riecke, and Joshua Singer. In this work, he used computational modeling in conjunction with patch-clamp electrophysiology to build and test realistic models of retinal cells, synapses, and circuits. Prior to this, Mark received his BSc in Mathematics from UBC, where he researched complex oscillatory behaviour of nonlinear partial differential equations.

Awards

Next Generation Leader, Allen Institute (1 of 6 selected worldwide in 2018). 2018-2021

Visiting Scientist, Janelia Research Campus, Howard Hughes Medical Institute. 2019.

Top nominated speaker award, Janelia Research Campus Annual Symposium. 2017.

Graduate Research Fellowship, National Science Foundation. 2009.

Postgraduate Scholar Award – Doctoral, Natural Sciences and Engineering Research Council of Canada. 2009.

University Scholar, Northwestern University Graduate School. 2009.

Multidisciplinary Visual Sciences Training Grant, National Institutes of Health. 2008.

Royal E. Cabell Fellowship, Northwestern University. 2007.

Science Scholar, University of British Columbia. 2007.

Undergraduate Student Research Award, Natural Sciences and Engineering Research Council of Canada. 2007.

Publications

Full list of publications available on Google Scholar.

1.      Cembrowski, M.S.#, Spruston, N.# Pyramidal cell diversity within and across the fields of the hippocampus. Nature Reviews Neuroscience, in review (invited submission).

2.      Cembrowski, M.S. #, Wang, L., Lemire, A., DiLisio, S.F., Copeland, M., Clements, J., Spruston, N. The subiculum is a patchwork of discrete subregions. eLife, in press.

3.      Cembrowski, M.S.#, Phillips, M.G., DiLisio, S.F., Shields, B.C., Winnubst, J., Chandrashekar, J., Bas, E., Spruston, N. # Dissociable structural and functional hippocampal outputs via distinct subiculum cell classes. Cell 173(5): 1280–1292, 2018.

4.      Bloss, E.B., Cembrowski, M.S., Karsh, B., Colonell, J., Fetter, R.D., Spruston, N. # Single excitatory axons form clustered synapses onto CA1 pyramidal cell dendrites. Nature Neuroscience 21(3): 353-363, 2018.

5.      Cembrowski M.S.#, Menon, V.# Continuous variation within cell types of the nervous system. Trends in Neurosciences 41(6): 339-350, 2018.

6.      Cembrowski, M.S. #, Spruston, N. Integrating results across methodologies is essential for producing robust neuronal taxonomies. Neuron 94(1): 747-751, 2017.

7.      Cembrowski, M.S.#, Spruston, N. Illuminating the neuronal architecture underlying context in fear memory. Cell 167(4): 888-889, 2016.

8.      Cembrowski, M.S., Wang., L., Sugino, K., Shields, B.C., Spruston, N. # Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons. eLife 5, 10.7554/eLife.14997, 2016.

9.      Bloss, E.B., Cembrowski, M.S., Karsh, B., Colonell, J., Fetter, R., Spruston, N. # Structured patterns of dendritic inhibition support branch-specific forms of integration in CA1 pyramidal cells. Neuron 89(5): 1016-1030, 2016.

10.  Cembrowski, M.S., Bachman, J.L., Wang, L., Sugino, K., Shields, B.C., Spruston, N. # Spatial gene-expression gradients underlie prominent heterogeneity of CA1 pyramidal neurons. Neuron 89(2): 351-368, 2016.

11.  Cembrowski, M.S. #, Logan, S., Tian, M., Jia, L., Li, W., Kath, W.L., Riecke, H., Singer, J.H. The mechanisms of repetitive spike generation in an axonless retinal interneuron. Cell Reports 1(2): 155-166, 2012.

Jarsky, T.*, Cembrowski, M.S.*, Logan, S., Kath, W.L., Riecke, H., Demb, J., Singer, J.H. # A synaptic mechanism for retinal adaptation to luminance and contrast. The Journal of Neuroscience 31(30): 11003-110515, 2011.

Office
3.353