Kavya Vinayan Pushpalatha
Molecular mechanisms of presynaptic long-term plasticity and its implications in synaptopathy
Kavya Vinayan Pushpalatha, Department of Neuroscience at University of Copenhagen, has received a Lundbeck Foundation Postdoc grant worth DKK 1.999.197.
About the project
Neuronal communication relies on action potential (AP)-induced presynaptic neurotransmitter (NT) release at release sites and on NT detection by the postsynaptic cells. To ensure stable signal transmission, this mode of communication must adapt to challenges.
Communication is endangered if postsynaptic cells become less NT-sensitive. To restore baseline transmission in this case, neurons induce a compensatory increase in the amount of NTs released per AP by activating a rescue mechanism known as presynaptic homeostatic potentiation (PHP). Synapses achieve this during sustaining challenges by increasing the local amounts of the conserved protein Unc18.
Human unc18 mutations are genetically linked to neurological disorders like epilepsy and Dravet syndrome, a fatal illness characterized by recurring seizures, which might implicate these symptoms are due to incapacitated long-term PHP. Despite its relevance for health and survival, the cellular and molecular mechanisms that sustain structural and functional synaptic changes during long-term PHP remain unresolved. To address this, I will combine established PHP assays with powerful methodology (genetics, electrophysiology, STED) in Drosophila as a model system. Unraveling key principles of long-term PHP will reveal how nervous systems across species persevere internal and external challenges (mutations, diseases, pollution), can aid define pathology mechanisms and contribute to the development of new therapies.
