MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Physiology

Background:

• Protease activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) are implicated in neurodegenerative diseases.
• PAR-1/MMP-1 signaling influences neuronal activity but its role in the ventral striatum is unclear.

Purpose of the Study:

• To investigate the role of MMP-1/PAR-1 signaling in regulating synaptic function of D1 and D2 spiny projection neurons (SPNs) in the ventral striatum.
• To assess the impact of altered MMP-1 levels on neuronal morphology and motor behavior.

Main Methods:

• Whole-cell recordings (WCR) were performed on D1 and D2 SPNs from control, MMP-1 overexpressing (MMP-1OE), and MMP-1OE/PAR-1 knockout (MMP-1OE/PAR-1KO) mice.
• Morphological analysis of D1 SPNs and behavioral tests assessing locomotor responses to amphetamine were conducted.

Main Results:

• MMP-1 overexpression increased spontaneous and miniature synaptic current frequency in D1 SPNs, an effect partially dependent on PAR-1.
• Dendritic complexity of D1 SPNs was increased in MMP-1OE mice, but not in MMP-1OE/PAR-1KO mice.
• MMP-1OE mice showed blunted locomotor responses to amphetamine, similar to MMP-1OE/PAR-1KO mice.

Conclusions:

• MMP-1 signaling, through both PAR-1 dependent and independent pathways, alters synaptic function in ventral striatal D1 neurons.
• These alterations may contribute to changes in neuronal activity and motor control observed in conditions affecting MMP-1/PAR-1 signaling.