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

Jessica Mitlöhner; Rahul Kaushik; Hartmut Niekisch; Armand Blondiaux; Christine E Gee; Max F K Happel; Eckart Gundelfinger; Alexander Dityatev; Renato Frischknecht; Constanze Seidenbecher

doi:10.3390/cells9020260

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

Standard

Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses. / Mitlöhner, Jessica; Kaushik, Rahul; Niekisch, Hartmut; Blondiaux, Armand; Gee, Christine E; Happel, Max F K; Gundelfinger, Eckart; Dityatev, Alexander; Frischknecht, Renato; Seidenbecher, Constanze.

In: CELLS-BASEL, Vol. 9, No. 2, 21.01.2020.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mitlöhner, J, Kaushik, R, Niekisch, H, Blondiaux, A, Gee, CE, Happel, MFK, Gundelfinger, E, Dityatev, A, Frischknecht, R & Seidenbecher, C 2020, 'Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses', CELLS-BASEL, vol. 9, no. 2. https://doi.org/10.3390/cells9020260

APA

Mitlöhner, J., Kaushik, R., Niekisch, H., Blondiaux, A., Gee, C. E., Happel, M. F. K., Gundelfinger, E., Dityatev, A., Frischknecht, R., & Seidenbecher, C. (2020). Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses. CELLS-BASEL, 9(2). https://doi.org/10.3390/cells9020260

Vancouver

Mitlöhner J, Kaushik R, Niekisch H, Blondiaux A, Gee CE, Happel MFK et al. Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses. CELLS-BASEL. 2020 Jan 21;9(2). https://doi.org/10.3390/cells9020260

Bibtex

@article{84f8d8022de446a78c98024f59776e86,

title = "Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses",

abstract = "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.",

author = "Jessica Mitl{\"o}hner and Rahul Kaushik and Hartmut Niekisch and Armand Blondiaux and Gee, {Christine E} and Happel, {Max F K} and Eckart Gundelfinger and Alexander Dityatev and Renato Frischknecht and Constanze Seidenbecher",

year = "2020",

month = jan,

day = "21",

doi = "10.3390/cells9020260",

language = "English",

volume = "9",

journal = "CELLS-BASEL",

issn = "2073-4409",

publisher = "MDPI Multidisciplinary Digital Publishing Institute",

number = "2",

}

RIS

TY - JOUR

T1 - Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses

AU - Mitlöhner, Jessica

AU - Kaushik, Rahul

AU - Niekisch, Hartmut

AU - Blondiaux, Armand

AU - Gee, Christine E

AU - Happel, Max F K

AU - Gundelfinger, Eckart

AU - Dityatev, Alexander

AU - Frischknecht, Renato

AU - Seidenbecher, Constanze

PY - 2020/1/21

Y1 - 2020/1/21

N2 - 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.

AB - 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.

U2 - 10.3390/cells9020260

DO - 10.3390/cells9020260

M3 - SCORING: Journal article

C2 - 31972963

VL - 9

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 2

ER -