Digital public defence: Tayyaba Qureshi
Cand.med Tayyaba Qureshi at Institute of Basic Medical Sciences will be defending the thesis “Elements of glutamate and GABA recycling at the synapse” for the degree of PhD (Philosophiae Doctor).
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Digital Trial Lecture – time and place
- First opponent: Professor David Krantz, University of California, Los Angeles
- Second opponent: Associate professor Brian Billups, Australian National University
- Third member and chair of the evaluation committee: Group Leader Camila Vicencio Esguerra, University of Oslo
Chair of the Defence
Professor Svend Davanger, University of Oslo
Professor Farrukh A. Chaudhry, University of Oslo
Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters, respectively, in the central nervous system. After exocytotic release from nerve endings and activation of specific postsynaptic receptors, sustained signaling requires efficient mechanisms for replenishment. The model of glutamate/GABA-glutamine cycle postulates that released glutamate and GABA are taken up by peri-synaptic astroglial processess, converted to glutamine, and subsequently shuttled back to neurons for re-synthesis. However, transporter proteins involved in the shuttling of glutamine from astroglial cells and into neurons and the accumulation of the neurotransmitters into synaptic vesicles have eluded characterization.
We have molecularly identified and characterized a “new” vesicular glutamate transporter, VGLUT3, and demonstrated previously unknown glutamate release from the axon terminals, dendrites and somas of not only glutamatergic neurons, but also non-glutamatergic neurons as well as astroglial cells. Thus, our data unravel novel modes of fast neurotransmission. Upon genetic inactivation of VGLUT1 we show that VGLUTs are associated with isoform-specific short-time plasticities and that VGLUT1 impacts synaptic vesicle biogenesis and recycling. During neuronal development, we demonstrate transient expression of VGLUTs contributing to morphogenesis.
We also show that the glutamine transporter Slc38a1 mediates astroglia-derived glutamine selectively into parvalbumin+ GABAergic neurons and sustains replenishment of the neurotransmitter pool of GABA and regulates synaptic vesicle dynamics. Slc38a1 also regulate cortical information processing and synaptic plasticity. Altogether, this thesis reveals unexpected function and regulation of several amino acid transporters which implicates essential roles in brain development and function. As glutamatergic and GABAergic signaling are involved in many diseases, our findings reveal potential therapeutic targets.
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