Place of work: Laboratory of Cell Biophysics
Type of recruitment: National Science Center Sonata BIS project
Scope of tasks:
Description of the role and the time-course of S-PALM in learning, memory and neuronal plasticity
The hallmark of the mammalian brain is the ability of processing and storing information in synapses and highly organized neuronal networks. The brain can adapt and change in response to various events under physiological conditions (i.e. learning) and pathophysiological conditions (i.e. epilepsy, stroke). Understanding the fundamental mechanisms of the plasticity of synaptic connections and neuronal network code lies in the center of contemporary neurobiology, neuropharmacology, and medicine. Targeting proteins to membranes is aided by covalent and reversible addition of fatty acids such as palmitic acid (S-palmitoylation). This modification may affect the membrane localization of the protein, protein activity and protein-protein interactions. We hypothesize this process plays a key role in learning and memory, because pharmacological modification of S-palmitoylation in rat nervous tissue abolished long-term synaptic potentiation, a substrate of memory formation. We have also discovered, that spatial learning in rats is associated with S-palmitoylation of specific neuronal proteins.
The project aims at describing the interaction of neurotransmitter dopamine and S-palmitoylation of synaptic proteins in the hippocampus- part of the brain playing crucial role in learning. In the team consisting of experts of various fields, we combine multiple experimental techniques: detection of modified proteins with mass spectrometry, genetic and pharmacological manipulation of activity of enzymes related to palmitoylation, behavioral analysis of learning in animals. We perform live recordings of electric signals from synapses, single neurons and neuronal networks and currents conducted by synaptic proteins to better understand the functional aspects of palmitoylated vs non-palmitoylated states.
Taking advantage of various experimental models and advanced quantitative methods we plan to address the following questions:
What is the role and time-course of S-palmitoylation in synaptic plasticity?
How dopamine affects S-palmitoylation of synaptic proteins?
What is the effect of S-palmitoylation of the function of proteins involved in learning and memory?
The results of this project will shed new light on the general mechanisms governing brain plasticity and may be also important for the understanding of dopamine role in brain physiology as well as planning new therapeutic strategies for the treatment of some neurological diseases.
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