Published: 13-06-2019 13:28 | Updated: 13-06-2019 13:42

New thesis on the role of SNAP-25 in processes important for learning and memory formation

Muhammad Irfan from the research group Growth and Metabolism will defend his thesis "Roles of SNAP-25 isoforms in activity-dependent long-term synaptic plasticity" on June 19th, 2019. Main Supervisor is Christina Bark

Muhammad Irfan

What's the main focus of your thesis?

The main focus of my thesis was to evaluate the role of a synaptic protein, SNAP-25, in processes important for learning and memory formation. SNAP-25 is expressed as two isoforms, SNAP-25a and SNAP-25, and I have assessed these ‘isoforms’ relative importance, as well as that of mutants of SNAP-25, in activity-dependent long-term potentiation (LTP) and depression (LTD) at hippocampal Schaffer collateral-CA1 synapses.

Which are the most important results?

The different variants of SNAP-25 regulate short- and long-term synaptic plasticity through its differential expression of two isoforms, SNAP-25a and SNAP-25b. The SNAP-25 isoforms are differently regulated between males and females in certain brain regions. These results can possibly be an indication, why we see sex differences in synaptic plasticity as well as in behavioral paradigms assessing cognitive functions, mood and motor coordination. We also initiated a study to investigate, how the metabolic syndrome can affect the brain expression of SNARE proteins, which include SNAP-25. Diet-induced metabolic impairments affected gene expression of SNARE proteins in different brain regions and also how the mice performed in behavioral tests.  

How can this new knowledge contribute to the improvement of people’s health?

Polymorphisms in the human gene for SNAP-25 are associated with both different traits and neuropsychiatric conditions. These polymorphisms likely affect the levels of SNAP-25 protein, or, which isoform of SNAP-25 that is expressed. Dynamic changes in the strength of synapses (synaptic plasticity) are viewed as a mechanism underlying the brain’s capability to learn and form memories. We have shown that the two isoforms of SNAP-25 contribute to this phenomenon differently at different stages of development; thus changed expression of the SNAP-25 isoforms can likely cause some of the traits and conditions found in humans. Similarly, changes in expression of synaptic SNARE proteins could possibly mediate the cognitive deficits associated with the metabolic syndrome.

What are your future ambitions?

My aim is to broaden my scientific expertise by continuing to work in collaborative national and international research projects. I will also like to create translational value for my basic scientific work in the future and work with human patients suffering from learning and memory disorders. 

Dissertation

Wednesday June 19th, 2019 at 13:00, Rolf Luft Auditorium L1:00

Thesis

Roles of SNAP-25 isoforms in activity-dependent long-term synaptic plasticity