ABOUT USSynaptic Neurobiology LabThe brain capacity to learn and remember grants the life experience and survival of living organisms. While there has been great advance in the field of neuroscience, there are still many unresolved questions at the molecular and system levels. Our laboratory aims to unravel novel molecular pathways that underlie neuronal plasticity during the process of learning and memory. Consequently, some of these pathways can help our understanding of the basis of cognitive deficit and neurological disorders.
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PROJECTSFrom synapses to nuclear signallingThe ability of neurons to modulate the strength of their connectivity, termed synaptic plasticity, remains the most attractive molecular correlate of learning and memory. Our laboratory integrates biochemical, molecular, cellular, and behavioural approaches, to gain deeper mechanistic insights of key cellular events in the pre- (presynaptic vesicle recycling) and post-synapses (glutamate receptor trafficking), as well as in the nucleus (RNA-mediated epigenetic regulation) that underpin synaptic plasticity, learning and memory. Ultimately, we aim to understand how dysregulation of these signalling pathways contributes to neurological disorders and neurodegenerative diseases.
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NEWS
Identification of a postsynaptic calcium sensor that controls activity-dependent AMPA receptor exocytosis
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The recruitment of synaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors underlies the strengthening of neuronal connectivity during learning and memory. This process is triggered by NMDA (N-methyl-D-aspartate) receptor-dependent postsynaptic calcium influx. In a new study published in Cell Reports (Tan and Jang et al., 2023), we report that the neuron-specific calcium-binding protein Copine-6 is a postsynaptic calcium sensor that controls the activity-dependent exocytosis of AMPA receptors during synaptic potentiation.
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AMPA receptor turnover in synaptic plasticity and cognition
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Post-translational ubiquitination of the GluA1 subunit marks AMPA receptors for degradation, but its functional role in vivo remains unknown. In a new study published in the Journal of Neuroscience (Guntupalli, Park and Han et al., 2023), we demonstrate that the GluA1 ubiquitin-deficient mice exhibit an altered threshold for synaptic plasticity accompanied by deficits in short-term memory and cognitive flexibility. Our findings suggest that activity-dependent ubiquitination of GluA1 fine-tunes the optimal number of synaptic AMPA receptors required for bidirectional synaptic plasticity and cognition in male mice.
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