Denis Burdakov group

Neural systems, metabolic control, sleep

How do organisms combine dynamic existence with stable health? What components are required (sensors, transistors, logic gates, and predictors)? What are their biological correlates? How is their function orchestrated to achieve unity of purpose and avoid malfunction? These basic questions can be studied in any bio-system. We currently focus on two: brain state control and metabolic balance in mammals. Not only are these areas of medical relevance (one in four people suffer from obesity and/or insomnia), they are also amenable to modern tools for observation and manipulation.

Unique protein make-up of cells mandatory for normal consciousness and energy balance allows us to target genes and labels to these cells. Inside complex and heterogeneous living tissue, we can thus discern and observe the dynamics of individual, molecularly-defined, cell systems - such as hypothalamic orexin/hypocretin neurons, which project both “up” and “down”, co-stimulate wakefulness and peripheral glucose fluxes, and protect from narcolepsy and obesity.

To probe the functional logic of fast interactions between cells, we use optogenetic tools for millisecond control of signals from specific neuronal types. We mostly work with transgenic mouse models and sometimes with computer-simulated virtual cells and cell systems. Ongoing projects use optogenetics, imaging, electrophysiology, anatomical tracing, immunolabelling and whole-body physiological assays to explore closely interrelated themes:

Figure 1:

Figure 1:

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TOP: immunolabelling showing orexin/hypocretin (green) and MCH (red) neurons in the lateral hypothalamus (from Burdakov & Alexopoulos, J Cell Moll Med 2005, 9(4):795). MIDDLE: schematic of the widespread projections of orexin/hypocretin (green) and MCH (red) neurons in the rodent brain. BOTTOM: model of direct regulation by glucose (from Burdakov et al, Philos Trans R Soc B 2005, 360(1464): 2227).

Figure 2:

Figure 2:

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TOP: viral insertion of cre-dependent ChR2 constructs (top left) into specific neurons allows the excitatory ion channel ChR2 to drive spikes and currents in response to blue light (top left traces). Cell images: genetic targeting of ChR2 can be confirmed by immunofluorescence combined with confocal microscopy: orexin neurons (red), ChR2-YFP (green), co-localization (yellow). BOTTOM: signal probing in native brain circuits by analyzing postsynaptic electrical responses of defined neurons to presynaptic optogenetic stimulation of specific sets of ChR2-containing axons (pictures contributed by Cornelia Schöne).

Collaborators

  • Professor Antoine Adamantidis, McGill
  • Professor Lars Fugger, Oxford
  • Drs Tania Korotkova and Alexei Ponomarenko, FMP-Berlin
  • Dr Lora Heisler, Cambridge
  • Dr John Apergis-Schoute, Cambridge

Selected publications

Our research themes

Click links to view others working on these themes

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