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Article

Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses

1
Leibniz Institute for Neurobiology (LIN), Department of Neurochemistry and Molecular Biology, 39118 Magdeburg, Germany
2
German Center for Neurodegenerative Diseases (DZNE), Molecular Neuroplasticity Group, 39120 Magdeburg, Germany
3
Center for Behavioral Brain Sciences (CBBS), 39120 Magdeburg, Germany
4
Leibniz Institute for Neurobiology (LIN), Department of Systems Physiology of Learning, 39118 Magdeburg, Germany
5
Center for Molecular Neurobiology Hamburg (ZMNH), Institute for Synaptic Physiology, 20251 Hamburg, Germany
6
Otto-von-Guericke University, Medical Faculty, 39120 Magdeburg, Germany
*
Authors to whom correspondence should be addressed.
Current address: Department of Biology, Animal Physiology, FAU Erlangen-Nürnberg, 91058 Erlangen, Germany.
Cells 2020, 9(2), 260; https://doi.org/10.3390/cells9020260
Received: 12 December 2019 / Revised: 14 January 2020 / Accepted: 17 January 2020 / Published: 21 January 2020
(This article belongs to the Special Issue Extracellular Matrix Remodeling 2019)
In the brain, Hebbian-type and homeostatic forms of plasticity are affected by neuromodulators like dopamine (DA). Modifications of the perisynaptic extracellular matrix (ECM), which control the functions and mobility of synaptic receptors as well as the diffusion of transmitters and neuromodulators in the extracellular space, are crucial for the manifestation of plasticity. Mechanistic links between synaptic activation and ECM modifications are largely unknown. Here, we report that neuromodulation via D1-type DA receptors can induce targeted ECM proteolysis specifically at excitatory synapses of rat cortical neurons via proteases ADAMTS-4 and -5. We showed that receptor activation induces increased proteolysis of brevican (BC) and aggrecan, two major constituents of the adult ECM both in vivo and in vitro. ADAMTS immunoreactivity was detected near synapses, and shRNA-mediated knockdown reduced BC cleavage. We have outlined a molecular scenario of how synaptic activity and neuromodulation are linked to ECM rearrangements via increased cAMP levels, NMDA receptor activation, and intracellular calcium signaling. View Full-Text
Keywords: ADAMTS 4/5; brevican; chondroitin sulfate proteoglycan; D1/D5 receptors; NMDA receptors ADAMTS 4/5; brevican; chondroitin sulfate proteoglycan; D1/D5 receptors; NMDA receptors
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MDPI and ACS Style

Mitlöhner, J.; Kaushik, R.; Niekisch, H.; Blondiaux, A.; Gee, C.E.; Happel, M.F.K.; Gundelfinger, E.; Dityatev, A.; Frischknecht, R.; Seidenbecher, C. Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses. Cells 2020, 9, 260. https://doi.org/10.3390/cells9020260

AMA Style

Mitlöhner J, Kaushik R, Niekisch H, Blondiaux A, Gee CE, Happel MFK, Gundelfinger E, Dityatev A, Frischknecht R, Seidenbecher C. Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses. Cells. 2020; 9(2):260. https://doi.org/10.3390/cells9020260

Chicago/Turabian Style

Mitlöhner, Jessica, Rahul Kaushik, Hartmut Niekisch, Armand Blondiaux, Christine E. Gee, Max F.K. Happel, Eckart Gundelfinger, Alexander Dityatev, Renato Frischknecht, and Constanze Seidenbecher. 2020. "Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses" Cells 9, no. 2: 260. https://doi.org/10.3390/cells9020260

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