Mark Cembrowski

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.

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.