EFFECTS OF NEUROMODULATION ON LOCAL PREFRONTAL CIRCUITS IN MOUSE MODELS FOR PSYCHIATRIC DISORDERS
Authors: Ikehara *Minobu , Yamamuro Kazuhiko , Noriyama Yuki , Saito Yasuhiko , Makinodan Manabu 
Published: February 2025

Abstract

Background
Neuromodulation has become a promising treatment approach for psychiatric disorders. Previous studies have suggested that repetitive transcranial magnetic stimulation(rTMS) may modulate neuronal activity and improve a variety of mental health conditions, including depression, catatonia, and insomnia, as well as hallucinations and obsessive-compulsive disorder, post-traumatic stress disorder, and drug abuse have also been suggested (Richter, 2023. Rashidi, 2017). However, its effects on diverse symptoms and the underlying mechanisms remain to be fully elucidated.

Aims & Objectives
This study aimed to investigate the effects of neuromodulation n depressive symptoms and social behavior using mouse models of social defeat stress, juvenile social isolation, and chronic restraint stress. Additionally, we sought to unravel the neurobiological mechanisms underlying these effects through electrophysiological measurements in the medial prefrontal cortex (mPFC), focusing on pyramidal cells, parvalbumin(PV) interneurons, and somatostatin(SST) interneurons. "

Method
In this study, we used deep brain stimulation, a neuromodulation technique, to locally stimulate the mPFC in mice because rTMS affects the entire brain. Social defeat stress, juvenile social isolation, and chronic restraint stress mouse models were utilized to evaluate the effects of neuromodulation on various dimensions, including depressive symptoms, social behavior, activity levels, and anxiety. Behavioral tests, including the 3-chamber test, open field test, and tail suspension test, were employed. Electrophysiological recordings were conducted using the whole-cell patch-clamp technique to measure excitatory and inhibitory postsynaptic currents in pyramidal cells, PV interneurons, and SST interneurons within the mPFC. Additionally, gamma oscillations in the brain's electroencephalogram were analyzed.

Results
Our findings demonstrated that neuromodulation not only ameliorated depressive symptoms but also improved social behavior in mouse models of psychiatric disorders. Electrophysiological investigations revealed that PV interneurons exhibited an increased frequency of excitatory postsynaptic currents and a decreased frequency of inhibitory postsynaptic currents following neuromodulation. Furthermore, a prolonged duration of gamma oscillations in the brain's electroencephalogram was observed. These results suggest that the activation of PV interneurons through neuromodulation contributes to improving depressive symptoms and social behavior.

Discussion & Conclusion
The present study highlights the efficacy of neuromodulation in alleviating depressive symptoms and enhancing social behavior in mouse models of psychiatric disorders.
Furthermore, our electrophysiological findings provide insights into the neurobiological mechanisms underlying these effects, specifically implicating the activation of PV interneurons within the mPFC. These findings contribute to our understanding of the potential of neuromodulation as a therapeutic intervention for psychiatric disorders and shed light on its underlying mechanisms.

References
Rashidi.S. 2017. Repetitive Transcranial Magnetic Stimulation in Psychiatric Disorders: A Review of Clinical Advances. Asian Journal of Pharmaceutics, (Suppl) 11 (2) S250
Richer.K, Kellner.S, Licht.C. 2023. rTMS in mental health disorders. Frontiers in Network Physiology, 28:3:943223