Lateral orbitofrontal dysfunction in the Sapap3 knockout mouse model of obsessive–compulsive disorder

Area of Science:

• Neuroscience
• Psychiatry
• Computational Neuroscience

Background:

• Obsessive–compulsive disorder (OCD) affects 2% of the population, with poorly understood neuropathophysiology.
• The orbitofrontal cortex (OFC) is implicated in OCD, but specific neuronal functional alterations remain unclear.

Purpose of the Study:

• To investigate detailed activity patterns in pyramidal neurons and interneurons in the lateral OFC.
• To analyze local field potential oscillations in an OCD mouse model.

Main Methods:

• In vivo multichannel recordings were performed in awake Sapap3 knockout (OCD model) and wildtype mice.
• Neuronal activity and oscillations were recorded in the lateral OFC during stationary periods to control for motor activity.

Main Results:

• Sapap3 knockout mice showed decreased OFC local field potential oscillation power, indicating network dysfunction.
• Putative interneurons exhibited increased activity, while pyramidal neurons showed enhanced bursting.
• Both neuron types displayed increased discharge variability and altered synchronization in the OCD model.

Conclusions:

• This study provides the first in vivo electrophysiological evidence of specific neuronal type alterations in the lateral OFC in an OCD mouse model.
• Findings enhance understanding of OCD neuropathophysiology and circuitry mechanisms.
• Results may inform hypotheses for potential OCD biomarkers.