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10 december 2018

Approved FOM programme 

Number 137.
Title Barriers in the brain: the molecular physics of learning and memory (BIB)
Executive organisational unit BUW
Programme management Prof.dr.ir. E.J.G. Peterman
Duration 2012-2016
Cost estimate M€ 1.8

The programme focuses on the molecular physical processes underlying regulation of synaptic strength, with special emphasis on spines: the transmitting end of synapses. In particular we aim to answer the following questions:

  1. What governs the morphodynamics of the spine neck?
  2. How does the spine neck affect 2-dimensional AMPA-receptor diffusion?
  3. Can the deformation of AMPA-receptor vesicles help to overcome the barrier posed by the spine neck?

Background, relevance and implementation
The human brain consists of more than one hundred billion neurons, intricately connected into functional neuronal circuits. These circuits enable us to feel, to express emotion, to sense the world around us, to move and to be creative. The basic structure of the neuronal circuitry is that of a network – individual neurons that interconnect at specialized cell-cell contact sites called synapses. At these sites, the action potential propagating along an axon (the long, transmitting protrusion of a neuron) triggers the release of small molecules – neurotrans­mitters – which in turn are sensed by the receiving cell using specialized receptor proteins embedded in the plasma membrane of dendrites (the receiving protrusions of neurons). Precise control of the development, connectivity and strength of synapses is critical for accurate neural network activity and normal brain function, including learning and memory formation. In fact, most of what we learn or remember is encoded – permanently or transiently - by modulating the strength of the specific synapses. By using an interdisciplinary approach, ranging from single-molecule biophysics in vitro and in vivo, via soft-matter theory, to neuronal cell biology, we seek to quantify the basic, physical processes that are at the heart of synaptic strength-regulation. We will focus on three aspects. First, we will unravel the molecular interactions that regulate the shape of the dendritic spine, the transmitting end of the synapse. Second, we will investigate how diffusion of neurotransmitter-receptors in the membrane is modulated by spine shape. Third, we will study how vesicles containing neuro­transmitters are transported by molecular motors and how barriers like the spine neck are overcome.

The final evaluation of this programme will consist of a self-evaluation initiated by the programme leader and is foreseen for 2016.

Please find a research highlight that was achieved in 2013 within this FOM programme here.