Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity.

Area of Science:

• Neuroscience
• Molecular Biology
• Extracellular Matrix Biology

Background:

• The adult brain's extracellular matrix (ECM) regulates neuronal plasticity, influencing recovery and mental health.
• Perineuronal nets (PNNs), condensed ECM structures rich in the proteoglycan aggrecan, are known to inhibit plasticity, but their precise role remains unclear.

Purpose of the Study:

• To investigate the functional role of aggrecan in PNNs and its impact on neuronal plasticity.
• To determine if aggrecan loss can reverse the developmental cessation of plasticity in the adult brain.

Main Methods:

• Developed a novel genetic model to conditionally and specifically delete the aggrecan (Acan) gene in adult mice.
• Assessed PNN structure, interneuron populations, ocular dominance plasticity, and object recognition memory following aggrecan deletion.

Main Results:

• Genetic ablation of aggrecan successfully removed PNNs, shifting parvalbumin-expressing interneurons to a high plasticity state.
• Selective aggrecan deletion in the visual cortex reinstated juvenile ocular dominance plasticity, mimicking critical period plasticity.
• Brain-wide aggrecan deletion improved object recognition memory.

Conclusions:

• Aggrecan is the primary functional component orchestrating PNNs.
• Loss of PNNs through aggrecan removal induces a permanent state of critical period-like plasticity in the adult brain.
• Targeting aggrecan offers a potential strategy for enhancing cognitive functions and recovery after brain injury.