Weilun Sun

Weilun Sun

PhD Student

DZNE – German Center for Neurodegenerative Diseases

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Alexander Dityatev Lab
Molecular Neuroplasticity,
DZNE – German Center for Neurodegenerative Diseases,
Madgeburg, Germany

Our studies demonstrate that attenuation of the neural ECM, particularly in the form of hyaluronic acid and chondroitin sulfate-rich perineuronal nets, is found in the ketamine model of schizophrenia and may result in epileptiform activity. The mechanisms underlying ECM attenuation involve an upregulation of the activities of matrix metalloproteinases, such as ADAMTS4/5 and MMP-9. They appeared to be under the control of dopaminergic and serotoninergic systems, involving D1-like and 5-HT7 receptors, respectively.

Our pioneering works revealed the role of ECM in synaptic plasticity. For example, tenascin-C supports induction of long-term potentiation (LTP) at CA3-CA1 synapses and the extinction of fear memories by regulation of L-type voltage-gated Ca2+ channels. Similarly, hyaluronic acid regulates synaptic plasticity through these channels. Another mechanism involves a control of axonal excitability by heparan sulfates. In vivo, heparinase treatment impairs context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta frequency band.