Axon initial segment ensheathed by extracellular matrix in perineuronal nets

Area of Science:

• Neuroscience
• Cell Biology
• Extracellular Matrix Research

Background:

• Perineuronal nets (PNNs) are extracellular matrix aggregates surrounding neurons.
• PNNs are composed of proteoglycans and are implicated in regulating synaptic plasticity.
• Their role around synaptic sites is well-studied, but less is known about their structure around non-synaptic axonal regions.

Purpose of the Study:

• To investigate the structural and cytochemical characteristics of PNNs around axon initial segments (AIS) that are largely devoid of synapses.
• To analyze the molecular composition of PNNs associated with large motoneurons in the mouse superior colliculus.
• To compare PNN composition across different neuronal domains and developmental stages.

Main Methods:

• Wisteria floribunda agglutinin (WFA) staining.
• Immunocytochemical detection of aggrecan and tenascin-R.
• Affinity-labeling of hyaluronan.
• Analysis in organotypic midbrain slice cultures.

Main Results:

• PNN molecular composition varied between different neurons but was consistent across somatodendritic and axonal domains of individual neurons.
• Synapse-poor AIS were covered by a continuous matrix sheath that infiltrated the surrounding neuropil.
• The periaxonal zone diameter often increased along the AIS.
• PNNs formed concomitantly around axonal and somatodendritic domains during the first three postnatal weeks.
• Key structural and molecular features were maintained in slice cultures.

Conclusions:

• PNNs form a continuous microenvironment around diverse neuronal domains, including synapse-poor AIS.
• The aggrecan-related extracellular matrix of PNNs likely plays a role in integrating and generating neuronal electrical activity.
• PNNs provide a consistent molecular milieu across different subcellular compartments of a neuron.