Martin Lauritzen – University of Copenhagen

Martin Lauritzen

Lab leader: Professor Martin Lauritzen

Office:
University of Copenhagen
Faculty of Health and Medical Sciences
Department of Neuroscience
Maersk Tower, room 07.04.23
Blegdamsvej 3
DK-2200 Copenhagen N
Denmark

Email: mlauritz@sund.ku.dk
Phone: +45 51298169

Websites: 
http://ribbdd.dk
http://www.cosbid.org

Research

Research in this laboratory concentrates on the neural and astrocytic mechanisms of local vascular regulation. Our basic research circles around blood flow control and blood-brain barrier properties under normal physiological conditions. In addition, we study aging, stroke and fast calcium waves that most commonly occur in disease states.  These waves exist as astroglial calcium waves (AGCW) that can be perceived as spatially restricted calcium rises in groups of astrocytes normally only 100 µm across and as cortical spreading depolarization waves (CSD) that involve both neurons and glia and propagate along the entire cortical mantle. Fast calcium waves are mechanistically involved in brain ageing, migraine, stroke, subarachnoid hemorrhage, intracerebral hematoma and traumatic brain injury.

Calcium imaging - dye injection in vivo

In order to study the physiological and pathophysiological mechanisms we use different methodologies that give information on different variables and scales. We use laser speckle contrast imaging to examine blood flow at the network level while we use two-photon microscopy to examine blood flow and permeability of single capillaries and penetrating arterioles.  In order to examine cellular regulation of blood flow we examine calcium dynamics in astrocytes and neurons, cell body and fine processes by use of organic or genetically encoded fluorescent calcium indicators.  We use multi electrode arrays to examine synaptic currents and oxygen electrodes to calculate brain energy metabolism. We also work to develop new methodologies that permit us to study the dynamics of cell organelles, i.e. conformational changes in organelles in relation to synaptic activity and in disease states. This is likely to reveal new disease mechanisms and new treatments based on an improved understanding of disease pathophysiology.  These developments promise to take two-photon microscopy one step further and may represent a way to obtain unprecedented spatial and temporal resolution in examination of the neurovascular unit and subcellular events in neurons and astrocytes in health and disease.

Key publications

  • Kucharz K, Lauritzen M. NMDA receptor-dependent endoplasmic reticulum fission-fusion accompanies rises in synaptic activity and cortical spreading depolarization waves. Brain 2018, in the press.
  • Lind BL, Jessen SB, Lønstrup M,  Charlène J, Bonvento G,  Lauritzen M.  Fast Ca2+ responses in astrocyte end-feet and neurovascular coupling in mice.  Glia. 2017 Oct 23. doi: 10.1002/glia.23246.
  • Thomsen K, Yokota T, Hasan-Olive MM, Sherazi N, Fakouri NM,  Desler C, Regnell CE,  Larsen S,  Rasmussen LJ, Dela F, Bergersen LH, Lauritzen M. Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.  Neurobiol Aging. 2017 Aug 12. pii: S0197-4580(17)30259-2. doi: 10.1016/j.neurobiolaging.2017.08.004.
  • Jessen SB, Mathiesen C, Lind BL, Lauritzen M.  Interneuron deficit associates attenuated network synchronization to mismatch of energy supply and demand in aging mouse brains. Cereb Cortex 2017, 27(1): 646-659.
  • Khennouf L, Gesslein B, Lind BL, van den Maagdenberg AM, Lauritzen M. Activity-dependent calcium, oxygen and vascular responses in a mouse model of familial hemiplegic migraine type 1. Ann Neurol. 2016 Aug;80(2):219-32.
  • Jessen SB, Brazhe A, Lind BL, Mathiesen C, Thomsen K, Jensen K, Lauritzen M:. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo. Cereb Cortex 2015;25:2594-2609.
  • Ayata C, Lauritzen M. Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature.  Physiol Rev. 2015, 95:953-93.   
  • Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O'Farrell FM, Buchan AM, Lauritzen M**, Attwell D**. Capillary pericytes regulate cerebral blood flow in health and disease. Nature 2014;508:55-60. **Co-corresponding authors
  • Lind BL, Brazhe AR, Jessen SB, Tan FC, Lauritzen M. Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo. Proc Natl Acad Sci U S A. 2013 Nov 11. 26;110(48):E4678-87.
  • Mathiesen C, Caesar K, Thomsen K, Hoogland TM, Witgen BM, Brazhe A, Lauritzen M. Activity-dependent Increases in Local Oxygen Consumption Correlate with Postsynaptic Currents in the Mouse Cerebellum In Vivo. Journal of Neuroscience. 14; 31(50):18327-37, 2011.
  • Attwell D, Buchan AM, Charpak S, Lauritzen M, MacVicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010, 468:232-243.