Perineuronal nets in the insular cortex shape salience-related behaviour in diabetes

Area of Science:

• Neuroscience
• Metabolic Disorders
• Extracellular Matrix Biology

Background:

• Diabetes mellitus is linked to central nervous system (CNS) functional connectivity changes and behavioral abnormalities.
• Perineuronal nets (PNNs), crucial for CNS network activity, surround parvalbumin-positive interneurons.
• Alterations in PNNs may underlie diabetes-associated behavioral deficits.

Purpose of the Study:

• To investigate the role of perineuronal nets (PNNs) in the behavioral abnormalities associated with diabetes.
• To determine how PNN density changes in specific brain regions in a mouse model of diabetes.
• To explore the causal relationship between PNNs in the insular cortex and diabetes-related behaviors.

Main Methods:

• Comparative analysis of PNN density in key brain regions (somatosensory cortex, medial prefrontal cortex, insular cortex, amygdala, reticular thalamic nucleus) between diabetic and control mice.
• Enzymatic degradation of PNNs in the insular cortex of diabetic mice.
• Behavioral testing including mechanical pain thresholds, risk-taking behavior, social interaction, and Place Escape/Avoidance Paradigm.

Main Results:

• Diabetic mice exhibited reduced PNN density in the somatosensory cortex and medial prefrontal cortex.
• Conversely, PNN density was increased in the insular cortex, amygdala, and reticular thalamic nucleus of diabetic mice.
• Enzymatic PNN degradation in the insular cortex normalized social interaction and Place Escape/Avoidance behaviors without affecting pain or risk-taking.

Conclusions:

• Diabetes induces region-specific alterations in PNN density within the CNS.
• Increased PNNs in the insular cortex causally contribute to altered salience attribution towards negative values in diabetes.
• Targeting PNNs in the insular cortex may offer a therapeutic strategy for diabetes-related behavioral changes.