Matthew Holt Lab

Research focus

​Astrocytes are the most abundant cell type in the mammalian central nervous system. In fact over 60% of the human brain is composed of astrocytes! Unfortunately, while we know that astrocytes are intimately associated with neuronal cell bodies and synapses their function(s) remain largely unknown. Are they acting merely as support cells, providing a supporting matrix for synapse formation, and providing substrates and energy for neurotransmission? Or are they directly influencing synaptic transmission by releasing and/or removing neuroactive substances from the synaptic cleft? A major obstacle to our understanding is that the basic signaling pathways used by astrocytes are only poorly understood.

The long-term goal of our group is to understand the molecular mechanisms that control development and function of astrocytes in vivo, and how they interact with neurons.
Our strategy is to use astrocytes isolated from mouse brain as a starting point. This allows us to effectively take a “bottom up” approach to astrocyte function. In a first step, we are combining state-of-the-art biochemical and physiological techniques (including quantitative mass-spectrometry and super-resolution fluorescence microscopy) to identify important protein and lipid signaling pathways in astrocytes, including their spatial and functional relationship to each other. In a second step, we will employ novel transgenic technologies to manipulate these pathways in vivo – with 2-photon based imaging techniques, and electrophysiological recordings in acute brain slices, allowing the study of astrocyte function in real-time.

As one astrocyte can actually contact 1000s of synapses from 100s of neurons, we believe that our in vivo approach will ultimately provide important insights into the function of neuronal circuits, which will impact on studies of learning and memory and behavior.

Interestingly, neurological conditions as diverse as Alzheimer’s disease, HIV and stroke are all characterized by massive synapse loss and failure of neuronal circuits. Many of the treatment strategies currently in development continue to specifically “target” neurons. This is surprising when understanding how astrocytes influence neuronal function represents a genuine alternative strategy. Astrocytes already know to keep neurons alive and working! As we determine the molecular mechanisms that underlie astrocyte function, we believe we will gain greater insights into the etiology of many neurological disorders, opening up exciting new therapeutic strategies.



Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and functionMuhammad K Reddy-Alla S Driller J. H Schreiner D Rey U Böhme M. A Hollmann C Ramesh N Depner H Lützkendorf J Matkovic T Götz T Bergeron D. D Schmoranzer J Goettfert F Holt Matthew Wahl M. C Hell S. W Scheiffele P Walter A Loll B Sigrist S.Versées WNature Communications, 6, 8362, 2015
One SNARE complex is sufficient for membrane fusionVan Den Bogaart G Holt M Bunt G Riedel D Wouters F. S Jahn RNATURE STRUCTURAL & MOLECULAR BIOLOGY, 17, 358-64, 2010
Synaptic vesicles are constitutively active fusion machines that function independently of Ca2+Holt M Riedel D Stein A Schuette C Jahn RCURRENT BIOLOGY, 18, 715-22, 2008
Molecular anatomy of a trafficking organelleTakamori S Holt M Stenius K Lemke E. A Gronborg M Riedel D Urlaub H Schenck S Brugger B. Ringler P Muller S. Rammner B Grater F Hub J. S De Groot B. L Mieskes G Moriyama Y Klingauf J Grubmuller H Heuser J Wieland F. T. Jahn RCELL, 127, 831-46, 2006

Job openings


New insights into how astrocytes help the brain process information

12/09/2019 - A collaboration between Vincent Bonin (NERF) and Matthew Holt (VIB-KU Leuven) reveals that noradrenaline plays a key role in how astrocytes – star-shaped cells in the brain closely associated with neurons – track distinct information during behavior.

9 VIB researchers received funding from the Alzheimer Foundation

21/03/2019 - VIB is very grateful to the Alzheimer Research Foundation for funding the researchers received, which helps them in their quest for cures. The ​Foundation has been fighting Alzheimer's disease for years and is working on a future without dementia.

Verge Genomics Announces Landmark Effort to Generate Field’s First Single Cell Data from Patients with Parkinson’s disease

21/05/2018 - In partnership with UC San Diego and VIB, Verge Genomics is leading an industry-academic consortium that will be the first to sequence gene expression in Parkinson’s patient brains at single cell resolution.

Matthew Holt

Matthew Holt

Research area(s)

Model organism(s)


PhD: MRC Laboratory of Molecular Biology, Cambridge, UK, 2002
Postdoc: MRC Laboratory of Molecular Biology, Cambridge, UK, 2002-03
Postdoc: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany, 2003-11
VIB Group leader since 2012

Contact Info

VIB-KU Leuven Center for Brain & Disease ResearchO&N 4, 6e verdCampus GasthuisbergHerestraat 49, bus 602 3000 LEUVENRoute description