The Role of the Medial Septum—Associated Networks in Controlling Locomotion and Motivation to Move

Abstract

The Medial Septum and diagonal Band of Broca (MSDB) was initially studied for its role in locomotion. However, the last several decades were focussed on its intriguing function in theta rhythm generation. Early studies relied on electrical stimulation, lesions and pharmacological manipulation, and reported an inconclusive picture regarding the role of the MSDB circuits. Recent studies using more specific methodologies have started to elucidate the differential role of the MSDB’s specific cell populations in controlling both theta rhythm and behaviour. In particular, a novel theory is emerging showing that different MSDB’s cell populations project to different brain regions and control distinct aspects of behaviour. While the majority of these behaviours involve movement, increasing evidence suggests that MSDB-related networks govern the motivational aspect of actions, rather than locomotion per se. Here, we review the literature that links MSDB, theta activity, and locomotion and propose open questions, future directions, and methods that could be employed to elucidate the diverse roles of the MSDB-associated networks.

The brain of the tree pangolin (Manis tricuspis). VIII. The subpallial telencephalon

“…The septal nuclear complex is often parcellated into four groups, several of which are divided into multiple nuclei, as well as the diagonal band of Broca (vertical and horizontal limbs, Ch2 and Ch3, respectively, of Geula et al, 2021); however, detailed architectonic and hodological studies reveal a far more complex organization of this subpallial region (e.g., Risold & Swanson, 1997;Paxinos et al, 2009;Radtke-Schuller, 2018). Our analysis of the septal nuclear complex in the tree pangolin revealed both a regional and nuclear organization very similar to that is known to be involved in locomotion, the generation of the theta rhythm in the hippocampus, and is also be involved in the motivation of undertaking actions (Mocellin & Mikulovic, 2021). The diagonal band of Broca is thought to be involved in memory retrieval (Liu & Gentleman, 2021) through the action of its projections upon the hippocampal formation (Roland et al, 2014).…”

Large-scale brain correlates of sweet versus cocaine reward in rats

“…It should be pointed that MS and vDBB comprise at least 3 neuronal populations (cholinergic, GABAergic and glutamatergic neurons [39]) that are heterogeneously distributed on the rostrocaudal axis. It is unlikely that MS-vDBB activation in the present study involved anxiety because ventral, but not dorsal hippocampus is required for anxiety-related behaviors [32,40]. In addition, this saccharin-induced activation probably does not reflect the appetite suppressive role of medial septal glutamatergic neurons because downstream neurons from the paraventricular hypothalamus (a brain region that largely suppresses feeding and which is activated by MS glutamatergic neurons [35]) were not activated here.…”

“…In both experiments, saccharin selectively activated the MS-vDBB subsystem of the septohippocampal system. MS-vDBB is a limbic structure involved in various cognitive and emotional processes, such as locomotion and motivational aspect of actions [32], arousal and attention [33], reward [34], feeding and consummatory behaviors [35,36], anxiety [37] and behavioral inhibition [38]. It should be pointed that MS and vDBB comprise at least 3 neuronal populations (cholinergic, GABAergic and glutamatergic neurons [39]) that are heterogeneously distributed on the rostrocaudal axis.…”

Basal Forebrain Impairment: Understanding the Mnemonic Function of the Septal Region Translates in Therapeutic Advances

“…Motivation, exploration and locomotion are behaviors that generally overlap, and the septal region is proposed to be one of the brain regions where the anatomical pathways involved in these behaviors intersect ( Mocellin and Mikulovic, 2021 ). Pharmacological inactivation or lesion of the medial septum in rodents has been shown to exert a powerful suppression of locomotion ( Oddie et al, 1996 ).…”

“…Pharmacological inactivation or lesion of the medial septum in rodents has been shown to exert a powerful suppression of locomotion ( Oddie et al, 1996 ). The involvement of the medial septum in the process of locomotion is reviewed in Mocellin and Mikulovic (2021) . The spiking rate of the rhythmically-bursting neurons cells is significantly correlated to the animal’s running speed ( King et al, 1998 ).…”