The role of the lateral septum in neuropsychiatric disease

Abstract

The lateral septum (LS) is a structure in the midline of the brain that is interconnected with areas associated with stress and feeding. This review highlights the role of the LS in anxiety, depression, and eating disorders and their comorbidity. There is a prevailing view that the LS is anxiolytic. This review finds that the LS is both anxiolytic and anxiogenic. Furthermore, the LS can promote and inhibit feeding. Given these shared roles, the LS represents a common site for the comorbidity of neuropsychiatric disorders, and therefore a potential pharmacological target. This is crucial since currently available treatments are not always effective. Corticotrophin-releasing factor 2 antagonists are potential drugs for the treatment of anxiety and anorexia and require further research. Furthermore, other drugs currently in trials for binge eating, such as alpha-adrenergic agonists, may in fact promote food intake. It is hoped that the advancements in chemo-and optogenetic techniques will allow future studies to profile the specific neural connections of the LS and their function. This information could facilitate our understanding of the underlying mechanisms, and therefore pharmacological targets, of these psychiatric conditions.

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections

“…Our data demonstrate that dLS GLP-1R neuron inhibition potentiates food intake without affecting changes in anxiety-like behavior and locomotion. Previous studies have shown that the projections from the lateral septum to thalamic nuclei mediate stress and anxiety-like behavior, including both anxiolytic and anxiogenic effects [36][37][38][39][40][41]. We found that manipulations of dLS neurons or their projections to the LHA failed to affect anxiety-like behavior while still influencing food intake.…”

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections

“…Our data demonstrate that dLS GLP−1R neuron inhibition potentiates food intake without affecting changes in anxiety-like behavior and locomotion. Previous studies have shown that the projections from the lateral septum to hypothalamic nuclei and the amygdala mediate stress and anxiety-like behavior, including both anxiolytic and anxiogenic effects [ [38] , [39] , [40] , [41] , [42] , [43] ]. We found that manipulations of dLS GLP−1R neurons or their projections to the LHA failed to affect anxiety-like behavior while still influencing food intake.…”

Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity

“…The LS is a structure that is interconnected with brain areas involved to cognition, motivation, autonomic regulation, stress and feeding ( Gray, 1977 ; Sheehan et al, 2004 ; Patel, 2022 ). It is part of a subcortical structure that delimits the midline of the brain called “septum” and is divided into two parts: the septum pellucidum and septum verum ( Andy and Stephan, 1968 ).…”