My postdoctoral work is focused on the classification and functional correlates of cell types in the mouse hippocampus. This work uses a combination of cell-type-specific next-generation RNA sequencing, in situ hybridization, viral circuit mapping, patch-clamp electrophysiology, chemogenetics, and behavioural assays in order to create coherent molecules-to-behaviour descriptions of neuronal populations. Currently, I am applying this approach to elucidate neuronal identity and function within the mouse subiculum, the main output population of the hippocampus1. Earlier in my postdoctoral research, I have applied similar classification approaches to phenotype CA1 pyramidal cells2 and other hippocampal principal cell types3 (see http://hipposeq.janelia.org), and as well have built computational models to study dendritic integration in CA1 pyramidal cells4,5.
Prior to my work at Janelia, I received my PhD in Applied Mathematics from Northwestern University. During graduate school, I used computational modeling in conjunction with patch-clamp electrophysiology to build realistic models of retinal cells, synapses, and circuits6,7.
Combining my experimental and computational backgrounds, I have devised a multidisciplinary methodology to deconstruct and assay the functional organization of neuronal populations (Fig. 1). In this paradigm, gene expression is characterized in the cell population of interest, and then mapped onto higher-order histological, physiological, and anatomical properties. The iterative combination of these techniques enables a rigourous cell-type deconstruction of the examined neuronal population. In turn, this classification then naturally lends itself to cell-type-specific functional interrogation, providing both marker genes for selective access and phenotype-derived hypotheses that can be tested through this access. I intend to use this approach unravel how the diversity of output neurons (CA1 and subiculum pyramidal cells) contributes to hippocampal-dependent behavior, as well as to elucidate how lesser-studied cell types contribute to hippocampal computation in health and disease (e.g., mossy cells; Fig. 2).
1. Cembrowski, M.S., Phillips, M.G., Spruston, N. Parallel output streams of the hippocampus. In preparation.
2. 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. Featured article of the issue, previewed by Tushev, G. and Schuman, E.M. Rethinking Functional Segregation: Gradients of Gene Expression in Area CA1. Neuron, 89(2):242-243, 2016.
3. 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.
5. Kim, Y., Hsu, C.-L., Cembrowski, M.S., Mensh, B.D., Spruston, N. Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons. eLife 4, doi:10.7554/eLife.06414, 2015.
6. 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. *: authors contributed equally
7. 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.