Levelt Group

TOP grant for Alzheimer research

Researchers Christiaan Levelt, Helmut Kessels and Wiesje van der Flier (VUMC) have been awarded a ZonMw TOP grant. They receive this grant for their project Synapses on high alert in Alzheimer’s disease. The project focuses on new mechanisms that are at the bottom of Alzheimer’s disease. The scientists receive a maximum of € 675,000 for this five-year research project.

Attention for synapses in Alzheimer’s disease

Alzheimer’s disease is characterized by plaques in the brain that contain the protein beta-amyloid. In the early stages of the disease, beta-amyloid causes memory and concentration problems because it affects the synapses, the points of contact between nerve cells. The researchers discovered earlier that beta-amyloid only attacks a certain type of synapses: those that are activated during attention. Now they will use advanced research techniques to investigate where in neural circuits of the mouse visual cortex these synapses are located, what their function is and whether memory and concentration problems in Alzheimer’s disease are caused by their selective loss. This project will expose a novel mechanism in Alzheimer’s disease and result in novel diagnostic approaches. The researchers hope that the insights they gain from this project will benefit the development of more targeted therapies that protect synapses in the early stages of Alzheimer’s disease.

About TOP

The aim of TOP Grants is to create room for innovative research of excellent quality. ZonMw considers this open boost for science to be THE innovation engine for the long term.



Levelt Group

Plasticity of the neocortex is crucial for us to learn and adapt to our environment. Once tasks or functions are learned, the brain can carry them out very efficiently, in a routine-like fashion. However, learning and carrying out routine functions do not go hand in hand. During development the brain is highly malleable, but processes information rather slowly and erratically. Vice versa, when we perform routine tasks, little learning occurs and we ignore many inputs. This situation can suddenly change when a routine procedure results in an unexpected outcome. We rapidly become aware of additional circumstances and learn what caused the unexpected result.

Recent evidence, also from our laboratory, suggests that these increases in plasticity levels during critical periods of development or in response to reinforcement signals are achieved by a temporary reduction in cortical inhibition. Possibly, high levels of inhibition increase performance of neuronal networks by suppressing inputs that are irrelevant for the execution of routine tasks. Reduced inhibition may support learning by allowing such inputs to be taken into consideration to solve a novel challenge.

Using the mouse visual cortex as a model, the Levelt lab studies how inhibition regulates cortical plasticity levels at the right time. To achieve this goal the lab employs a combination of state-of-the art two-photon microscopy, electrophysiology, optogenetics and gene manipulation.

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