Abstract: Man Ho WONG

Functional analysis of MAGUK proteins in Ocular Dominance Plasticity

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Man Ho Wong (1), Xiaojie Huang (1, 2), Oliver Schlüter (1)

(1) European Neuroscience Institute, Göttingen, germany
(2) GGNB doctoral program “Molecular Physiology of the Brain”, Götingen, Germany

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Synaptic plasticity involves in many cognitive functions, such as learning and memory. To understand how the brain works, it is essential to study the mechanisms of synaptic plasticity. Membrane-associated guanylate kinases (MAGUKs) are a family of scaffold proteins important for the regulation of glutamate receptor expression at the synapse, and hence they play a key role in the synaptic transmission. In my project, I use an experimental model of developmental plasticity, ocular dominance plasticity (ODP), to study their role in synaptic transmission. During development, ODP vanishes after the critical period when the local inhibitory neuronal network in the visual cortex matures. This maturation involves the changes of synaptic transmission. We found that a MAGUK protein, PSD-95, is involved in the regulation of synaptic transmission of excitatory synapses onto the principal neuron of the network. Interestingly, we also found that knocking out PSD-95 has a different effect in the synaptic transmission of excitatory synapses onto the inhibitory interneuron of the network. The role of PSD-95 in interneuron as well as the global role of PSD-95 in the network are still unknown. To investigate the functions of PSD-95 and other MAGUK proteins in this neuronal network, I study their roles in synaptic transmission with patch-clamp electrophysiology. The regulation of glutamate receptor expression at the synapses onto the principal neurons and interneurons is studied. Since the synchronization of synaptic transmission might be important for the long-range connections in the brain, the role of PSD-95 in the regulation of AMPA receptor kinetics is studied. MAGUKs’ role in long term plasticity and the neuronal connectivity of the inhibitory network will also be studied. Besides visual cortex, this kind of neuronal network can also be found in other cortical areas. The activity of this network is important for the proper functioning of the brain. Investigation on the roles of MAGUKs in this network will help us to understand better how the brain functions.