During learning, reversible physiological changes in synaptic transmission take place in the central nerve system (CNS). These changes must then be stabilized or consolidated in order for memory to persist. Much evidence indicates that memories are created by alterations in glutamate-dependent excitatory synaptic transmission. The creation of stable, persistent changes (long-term memory - LTM) requires gene expression and protein synthesis. However, molecular changes are transient and so, on their own, are insufficient to explain LTM. It is well accepted that structural changes in synaptic morphology, occurring either consequent to protein synthesis or parallel with it are also necessary. The three dimensional structural organization of dendritic spines was n ever investigated at the molecular level.
The research proposed here aims to investigate the 3D organization of dendritic spines using cryo electron tomography at different stages of neuronal growth and in response do various neuronal stimuli. Within the tomograms, methods will be devoted for labelling and identification of macromolecular complexes. The combination of cryo electron tomography and the development of novel methods for intracellular macromolecular complex identification will give us deeper insight into structural mechanisms associated with LTM. Cryo electron tomography is the tool of choice for structural investigation at the molecular level of intact cells preserved in their native environment in a frozen-hydrated state.
Field of science
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /natural sciences/physical sciences/optics/microscopy/electron microscopy
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