Aberrant perineuronal nets alter spinal circuits, impair motor function, and increase plasticity

Area of Science:

• Neuroscience
• Extracellular Matrix Biology
• Spinal Cord Injury Research

Background:

• Perineuronal nets (PNNs) are specialized extracellular matrices crucial for brain function, stabilizing synapses and modulating plasticity.
• While cortical PNN roles are known, the function of spinal PNNs, particularly around motoneurons, remains largely uncharacterized.

Purpose of the Study:

• To investigate the role of spinal PNNs in motor function and plasticity.
• To elucidate the impact of PNN disorganization on spinal circuits in both healthy and injured states.

Main Methods:

• Utilized transgenic mice lacking cartilage link protein 1 (Crtl1 KO mice) with PNN assembly defects.
• Conducted behavioral tests and electrophysiological recordings in intact and spinal cord-injured mice.
• Analyzed PNN structure and excitatory synapse distribution around spinal motoneurons.

Main Results:

• Crtl1 KO mice exhibited disorganized PNNs and altered PNN component proportions in the motor cortex and spinal cord.
• These mice displayed motor impairments and hyperexcitability of spinal reflexes compared to wild-type controls.
• Spinal cord injury in Crtl1 KO mice led to increased contralateral axonal sprouting, suggesting a permissive environment for regeneration.

Conclusions:

• The absence of Crtl1 leads to aberrant PNNs, disrupting motoneuron physiology and spinal circuit function, resulting in motor deficits.
• Disorganized PNNs alter excitatory synapse balance around motoneurons.
• Aberrant PNNs create a permissive environment for axonal sprouting following spinal cord injury, potentially influencing recovery.