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Combining holographic optogenetics and STED microscopy for studying synaptic plasticity in Alzheimer ’s disease


Start Date
End Date
Total Funding
€ 193 595
Funding Programme
European Countries Involved
New perspectives are opening in neuroscience: the era of electricity is transitioning into the era of light. Super-resolution microscopy was elected “Method of the year 2008” and optogenetics “Method of the year 2010” by the Journal Nature Methods. HOLOSTED is a biophysics project using these modern optical methods to study the effects of Alzheimer’s disease (AD) on synaptic plasticity. It has two general objectives: First, improving optical methods, including STED (STimulated Emission Depletion) microscopy and wavefront shaping. For the first time, digital holography will be combined with STED microscopy. This will enable precise control of synaptic signaling and the simultaneous analysis of the neuronal response with high spatial and temporal resolution. Second, progressing the understanding of AD by examining - on the level of single dendritic spines - the role of Amyloid beta, a central protein in AD, in compromising synaptic plasticity. The potential of certain drugs to rescue plasticity will be tested. HOLOSTED provides training through research: The host, a leading lab in wavefront engineering for neuronal stimulation, will teach the fellow digital holography for optical stimulation of neurons by optogenetics or neurotransmitter uncaging. The fellow will not only be trained in physical methods, but also in biological application. Besides optics, he will learn neurophysiology and -pathology. Together with his background in super-resolution imaging this training will enable him to create a profile in Functional Super-Resolution Imaging for becoming an independent group leader. HOLOSTED creates genuine mobility and thereby enables the fellow to transfer expertise of super-resolution microscopy to France and, upon his return, competence about targeted stimulation and optogenetics to Germany. Favored by contacts from previous stays in different countries (Greece, USA, Germany) the fellow will tighten scientific and personal relationships between peoples.'
Project partners
Centre National De La Recherche Scientifique Cnrs
Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).