The Medial Septum as a Potential Target for Treating Brain Disorders Associated with Oscillopathies

Abstract

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies

“…We thank the members of the Department of Physiology, Osaka City University Graduate School of Medicine for fruitful discussions. The preprint of this paper has been posted in Preprints (Takeuchi et al, 2021b).…”

The role of the lateral septum in neuropsychiatric disease

“…Therefore, this may be a potential mechanism by which NMDAR antagonists exert their anxiolytic and antidepressive effects. Nevertheless, the remainder of this review will focus on the role of the LS in mood disorders, as the role of the medial septum in these disorders has recently been comprehensively reviewed by Takeuchi and colleagues (Takeuchi et al, 2021).…”

“…It is thought that the dense population of glutamatergic neurons within the MS plays an important role in the generation of these theta rhythms (Robinson et al, 2016). As well as their role in learning and memory, recent evidence suggests a role of theta oscillations | 1423 PATEL in the regulation of mood (Takeuchi et al, 2021). For example, theta rhythms are augmented in anxiogenic environments (Adhikari et al, 2010) and patients with major depressive disorder show elevated theta rhythm EEG activity (Newson & Thiagarajan, 2019).…”

“…Nevertheless, the remainder of this review will focus on the role of the LS in mood disorders, as the role of the medial septum in these disorders has recently been comprehensively reviewed by Takeuchi and colleagues (Takeuchi et al, 2021).…”

Dynamic evaluation of induced epilepsy in rats: a bayesian network perspective

“…A study carried out by TAKEUCHI et al (2021) supports the suggestion of the Septum-Hippocampal pathway as an important factor playing a role in abnormal oscillations, in the Theta band of Local Field Potentials inside the context of the mechanisms to disrupt epileptic seizures. Furthermore, the study suggests the area as vital to treat the disease and restore the brain to its regular patterns of brain rhythms oscillation.…”