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.

A Novel Bayesian Linear Regression Model for the Analysis of Neuroimaging Data

“…Similar volumetric abnormalities have also been reported for the animal model used in this study [24,45]. In addition, the method also detected the medial septum, which plays a significant role in dopamine-related disorders such as schizophrenia [46,47] and addictions [48][49][50], which highlights the relevance of this structure in mental disorders. Regarding WM, the method found three well-defined brain areas, the frontal part of corpus callosum and WM tracts of the brainstem and the cerebellum [51,52].…”

Functional Neuroanatomy of the Rat Nucleus Incertus–Medial Septum Tract: Implications for the Cell-Specific Control of the Septohippocampal Pathway

“…MS neurons are under modulatory influences from several brain areas, including ascending cholinergic projections from the dorsolateral tegmental nucleus, serotonergic projections from the raphe nuclei, adrenergic inputs from the locus coeruleus (Takeuchi et al, 2021) and a dense projection from the brainstem, nucleus incertus (NI), an enigmatic structure involved in the control of contextual memories, locomotor speed, arousal, and stress responses (Ma et al, 2013(Ma et al, , 2017aSzőnyi et al, 2019;Lu et al, 2020).…”

Ameliorative Processes of Beta-Carotene in Streptozotocin-Induced Diabetic Vascular Dementia in Rats

“…The septohippocampal loop with cholinergic synapses and cholinergic transmission function are important for neuroplasticity and neurodegeneration [54]. The literature revealed that BC has a high binding capacity toward AChE, and it attenuated cognitive dysfunction in a mice model of AD [42].…”