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Hongyu Zhang
Department of Biomedicine, University of Bergen

Loss of synapses has been associated with cognitive decline in a variety of neurodegenerative and psychiatric disorders. This has been attributed, at least partially, to the loss of synaptic AMPA-type glutamate receptors (AMPARs), which mediate the majority of fast excitatory neurotransmission in the central nervous system. AMPARs can be reversibly trapped at the synapse; however, it remains largely unexplored how to modulate AMPAR synaptic trapping and reverse memory deficits in diseases. Using a combination of live-cell single nanoparticle tracking, super-resolution imaging, electrophysiology and behavioral tests, we have demonstrated that pharmacological reversal of AMPAR synaptic trapping using an antidepressant tianeptine restored synaptic plasticity and memory in different rodent models of Huntington’s disease and stress/depression. One exciting piece of ongoing work is that we have developed a small interfering peptide, which potentiated AMPAR synaptic trapping and reversed chronic stress-induced memory deficits in mice. Next, we will explore the effects of this peptide in Alzheimer's models and develop an optogenetically-controlled peptide to spatiotemporally control AMPAR synaptic trapping during the various stages of induction, establishment, and consolidation of synaptic plasticity, and different stages of memory.

References:

1. Zhang H* et al., Nat Commun (Journal Impact factor: 17.7). 2018 Oct 15;9(1):4272.Ìý* Corresponding author
2. Zhang H, et al., Mol Psychiatry (Journal Impact factor: 13.4). 2013 Apr;18(4):471-84.
3. Zhang H*, Bramham CR*. Eur J Neurosci. 2020 Sep 5.Ìý* Corresponding author; Top cited article in Eur J Neurosci. 2020-2021
4. Zhang H*^#, Bramham CR*. Front Synaptic Neurosci. 2020 Jul 10;12:26. * Corresponding author, # Lead contact

Chairperson:ÌýClive Bramham, Department of Biomedicine