Glutamatergic neurons and GABAergic neurons of medial prefrontal cortex control hoarding-like behavior

Area of Science:

• Neuroscience
• Psychiatry
• Behavioral Science

Background:

• Hoarding disorder (HD) is a chronic condition with complex origins, including possessiveness and neurocognitive factors.
• The specific neural mechanisms underlying excessive hoarding behavior in HD remain largely unelucidated.
• Understanding the neurobiology of HD is crucial for developing effective therapeutic interventions.

Purpose of the Study:

• To investigate the role of specific neuronal activities within the medial prefrontal cortex (mPFC) in driving hoarding-like behaviors.
• To identify potential neural targets for therapeutic modulation in hoarding disorder.

Main Methods:

• Utilized viral infections and ex vivo brain slice electrophysiology recordings in a mouse model.
• Employed chemogenetic manipulation to selectively alter glutamatergic and GABAergic neuronal activity in the mPFC.
• Assessed the impact of these manipulations on hoarding-like behavioral responses.

Main Results:

• Increased glutamatergic neuronal activity and decreased GABAergic neuronal activity in the mPFC were correlated with accelerated hoarding-like behavior.
• Chemogenetic reduction of glutamatergic activity or enhancement of GABAergic activity significantly improved hoarding-like behaviors.
• These findings pinpoint specific neuronal populations in the mPFC critical for hoarding behavior.

Conclusions:

• Alterations in the balance of glutamatergic and GABAergic neuronal activity within the mPFC are key contributors to hoarding-like behavior.
• Targeted neuromodulation strategies focusing on these specific neuronal types offer a promising avenue for future HD therapies.
• This research provides a foundation for developing precise, mechanism-based treatments for hoarding disorder.