Dr Mahesh Miikael Karnani

Personal profile

• 2024 - present: Chancellor’s Fellow, University of Edinburgh
• 2020 - 2024: Assistant Professor, VU Amsterdam
• 2016 - 2020: Postdoctoral Research Fellow, The Francis Crick Institute, KCL, ETHZ
• 2012 - 2015: Postdoctoral Research Fellow, Columbia University
• 2012: PhD University of Cambridge
• 2008: MSc University of Helsinki

Research Themes

Synapses, Circuits and Behaviour 

Signalling, Homeostasis and Energy Balance      

Research

We study how behavioural drives, primarily feeding, are regulated by hypothalamic and cortical neurons. The lateral hypothalamus is a key controller of feeding and other motivated behaviours. We recently discovered that it contains barely any synaptically connected microcircuits, which are ubiquitous in the cortex. On the other hand, key parts of the cortex send input to the lateral hypothalamus. We study these neural pathways with slice electrophysiology and in vivo calcium imaging.

Figure 1: Lateral hypothalamic orexin neurons control locomotion in response to internally generated impulses as well as sensory stimuli. For more information, see https://doi.org/10.1016/j.pneurobio.2020.101771  

Figure 2: Lateral hypothalamic neurons do not form densely connected local microcircuits. Background micrograph shows GAD65 neurons in green and MCH neurons in magenta. For more information, see https://doi.org/10.1016/j.cub.2020.07.061

Relevant publications

Primary research:

Burdakov, D. & Karnani, M.M. Ultra-sparse synaptic connectivity in the lateral hypothalamus. Current Biology 30(20): 4063-4070.e2 https://doi.org/10.1016/j.cub.2020.07.061 (2020).

Karnani, M.M., Schoene, C., Bracey, E., Viskaitis, P., Gonzalez, J.A., Adamantidis, A. & Burdakov, D. Role of Spontaneous and Sensory Orexin Network Dynamics in Rapid Locomotion Initiation. Progress in Neurobiology, 187, 101771 https://doi.org/10.1016/j.pneurobio.2020.101771 (2020).

Jackson, J., Karnani, M.M., Zemelman, B.V., Burdakov, D. & Lee, A.K. Inhibitory control of Prefrontal Cortex by the Claustrum. Neuron 99, 1029-1039 https://doi.org/10.1016/j.neuron.2018.07.031 (2018).

Karnani, M.M., Jackson, J., Ayzenshtat, I., Tucciarone, J., Manoocheri, K., Snider, W.G. & Yuste, R. Cooperative Subnetworks of Molecularly Similar Interneurons in Mouse Neocortex. Neuron 90:86-100 https://doi.org/10.1016/j.neuron.2016.02.037 (2016).

Karnani, M.M., Jackson, J., Ayzenshtat, I., Hamzei-Sichani, A., Manoocheri, K. & Yuste, R. Opening Holes in the Blanket of Inhibition: Localized Lateral Disinhibition by VIP Interneurons. J Neurosci 36:3471-80 https://doi.org/10.1523/JNEUROSCI.3646-15.2016 (2016).

Karnani, M.M., Szabó, G., Erdélyi, F. & Burdakov, D. Lateral hypothalamic GAD65 neurons are spontaneously firing and distinct from orexin and MCH neurons. J Physiol 591, 933-53 https://doi.org/10.1113/jphysiol.2012.243493 (2013).

Karnani, M.M., Apergis-Schoute, J., Adamantidis, A., Jensen, L.T., de Lecea, L., Fugger, L. & Burdakov, D. Activation of central orexin/hypocretin neurons by dietary amino-acids. Neuron 72, 616-29 https://doi.org/10.1016/j.neuron.2011.08.027 (2011).

Preprints:

Hartmann, C., Mahajan, A., Borges, V., Razenberg, L., Thönnes, Y. & Karnani, M. M. The Switchmaze: an open-design device for measuring motivation and drive switching in mice. BioRxiv (2024) https://doi.org/10.1101/2024.01.31.578188

Viskaitis, P., Tesmer, A.L., Karnani, M.M., Arnold, M., Donegan, D., Bracey, E.F., Peleg-Raibstein, D. & Burdakov, D.  Arousal neurons that anticipate deviations in blood glucose. BioRxiv (2022) https://doi.org/10.1101/2022.04.14.488310

Reviews:

Mercier, M.S., Magloire V. & Karnani, M.M., Enhancing scientific dissemination in neuroscience via preprint peer-review: “Peer Community In Circuit Neuroscience”. Neuroanatomy and Behaviour 2 (2020) https://doi.org/10.35430/nab.2020.e9

Karnani, M.M. & Jackson, J. Interneuron Cooperativity in Cortical Circuits. The Neuroscientist 4, 329-341 https://doi.org/10.1177/1073858417733719 (2018).

Karnani, M.M., Agetsuma, M. & Yuste R. A blanket of inhibition: functional inferences from dense inhibitory connectivity. Curr Opin Neurobiol 26C, 96-102 https://doi.org/10.1016/j.conb.2013.12.015 (2014). See cover illustration.

Module releases:

Hartmann, C. & Karnani, M.M. Sensing water dispenser for rodent work using Arduino and Raspberry Pi. ResearchEquals – Equipment (2023) https://doi.org/10.53962/g2r8-ysds

Hartmann, C., Thönnes, Y. & Karnani, M.M. Timed running wheel for rodent work using Arduino and Raspberry Pi. ResearchEquals – Equipment (2023) https://doi.org/10.53962/j5fx-4zy8

Hartmann, C., Thönnes, Y. & Karnani, M.M. Single entry module for rodent work using Arduino and Raspberry Pi. ResearchEquals – Equipment (2023) https://doi.org/10.53962/ryj7-rtqw

Karnani, M.M. Next steps in automated handler-free behavioural recordings: spatially discretized behavioural cycles. ResearchEquals – Idea (2023) https://doi.org/10.53962/q2za-3hkc

Karnani, M.M. Measuring motivation and drive switching in rodents – why and how? ResearchEquals – Idea (2023) https://doi.org/10.53962/jcc3-qsaa

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here