Lab Website: https://icnlabs.org
Animal cognition is a complex dynamic process that is tightly controlled by feed-forward and feed-back mechanisms and involves the concerted action of multiple distinct excitatory and inhibitory neuron types in the brain. Modern genetic and optical tools enable the targeted identification, stimulation, or recording of a single neuron type at a time. However, how the activation dynamics of multiple neuron types converge in real-time and how these time-varying interactions impact network output to influence the cognitive outcome are unknown. Using single-neuron, single-spike resolution, multi-population voltage imaging in mice, during selective attention paradigms adapted from primates, my research program will examine the synergistic dynamics of targeted cortical neurons in behavior and cognitive function. We will further combine this approach with targeted gene perturbation to understand the contribution of risk genes to impaired circuit function, which may in turn contribute to some of the cognitive deficits associated with psychiatric illnesses.
Madhu Kannan is an Assistant Professor of Neuroscience and a member of the Medical Discovery Team on Optical Imaging and Brain Science.
Dr. Kannan completed her undergraduate studies in Biochemistry in Chennai, India, and acquired a Master’s in Molecular Genetics at the University of Leicester, UK. She then obtained a Ph.D. in Neurophysiology at the Max Planck Institute of Experimental Medicine and George August University, in Germany. During her postdoctoral work, in the lab of Dr. Mike Higley at Yale School of Medicine, CT, she studied the mechanisms of experience-dependent plasticity at cortical inhibitory synapses using slice electrophysiology and optogenetics. She subsequently joined the lab of Dr. Vincent Pieribone, for a second postdoc, where she created a suite of mutually compatible recombinant voltage indicators and used them to perform some of the first recordings, with millisecond resolution, of the correlated dynamics of genetically distinct neuron types in cortical microcircuits in behaving rodents.
- C Huang†, J Luo, S J Woo, L A Roitman, J Li, V A Pieribone, M Kannan†, G Vasan†, M J Schnitzer†. Dopamine signals integrate innate and learnt valences to regulate memory dynamics. Research-Square; under revision in Nature. †Corresponding authors.
- M Kannan*†, G Vasan*†, S Haziza*, C Huang, R Chrapkiewicz, J Luo, J A Cardin, M J Schnitzer† and V A Pieribone†. Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types. Science, 378(6619), 2022. *Equal contribution. †Corresponding authors.
- M Kannan, G Vasan, and V A Pieribone. Optimizing strategies for developing genetically encoded voltage indicators. Frontiers in Cellular Neuroscience, 13:53, 2019.
- M Kannan*, G Vasan*, C Huang, S Haziza, J Z Li, H Inan, M J Schnitzer, and V A Pieribone. Fast, in vivo voltage imaging using a red fluorescent indicator. Nature Methods, 15(12):1108–1116, 2018. *Equal contribution. Highlighted in Yale News.
- M Kannan, G G Gross, D B Arnold, and M J Higley. Visual deprivation during the critical period enhances layer 2/3 GABAergic inhibition in mouse V1. Journal of Neuroscience, 36(22):5914–5919, 2016.
- A Matz, S Lee, N S Domeyer, D Zanini, A Holubowska, M Kannan, M Farnworth, O Jahn, M C Gopfert, and J Stegmüller. Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157. Cell Death and Differentiation, 22(4):626–642, 2015.
- C Mukherjee, A Holubowska, N S Domeyer, M Mitkovski, S Lee, M Kannan, A Matz, M Vadhvani, and J Stegmüller. Loss of the neuron-specific f-box protein FBXO41 models an ataxia-like phenotype in mice with neuronal migration defects and degeneration in the cerebellum. Journal of Neuroscience, 35(23):8701–8717, 2015.
- M Kannan, S Lee, N S Domeyer, and J Stegmüller. The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase Smurf1 in the control of axon growth. Development, 139(19):3600– 3612, 2012.
- M Kannan, S Lee, N S Domeyer, T Nakazawa, and J Stegmüller. p250GAP is a novel player in the Cdh1-APC/Smurf1 pathway of axon growth regulation. PLoS One, 7(11), 2012.
- M Kannan, J R Steinert, I D Forsythe, A G Smith, and T Chernova. Mevastatin accelerates loss of synaptic proteins and neurite degeneration in aging cortical neurons in a heme independent manner. Neurobiology of Aging, 31(9):1543–1553, 2010.