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Medial Septum and Magnocellular Basal Forebrain: Cellular Function, Pathology and Behavior

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Neurons of the medial septum and magnocellular basal forebrain (MS-MBF) are the main source of cholinergic transmission to the hippocampus, amygdala and cortex. In addition, the MS-MBF contains GABAergic and glutamatergic neurons that equally project to those structures. Altogether, this system contributes to ...

Neurons of the medial septum and magnocellular basal forebrain (MS-MBF) are the main source of cholinergic transmission to the hippocampus, amygdala and cortex. In addition, the MS-MBF contains GABAergic and glutamatergic neurons that equally project to those structures. Altogether, this system contributes to the modulation of cognitive and emotional functions associated to those telencephalic areas. Dysregulation of this circuitry results in important neurological deficits including epilepsy and Alzheimer disease (AD).
The present topic aims to collect frontier research in understanding MS-MBF structure, function and physiopathology bringing together, in a single issue, recent advances from different methodological approaches.
Unlike other neural structures, the MS-MBF does not have a clear border that allows differentiation from adjacent structures. Nissl labelling shows large intensely stained neurons within the region. But, but several groups of neurons stained with protein markers shows that they are not necessarily contained within the MS-MBF boundaries. In addition to cytoarchitectonics, the pattern of connections of this region is not completely elucidated under the use of new tracing methods. Understanding the neuronal phenotypes belonging to the MS-MBF and its pattern of connections will help to elucidate how MS-MBF regulates upper telencephalic structures. Moreover, this information brought together will cast light on how these structures may work together in particular cerebral functions.
The medial septum has been considered as the main pacemaker of the hippocampal theta rhythm. Although this vision has been challenged and the hippocampus may enter in theta loops even in the absence of septal control, the hippocampus and septum are usually phase locked when entering in theta. Thus, the whole system must be considered when studying theta generation. Considering the fact that hippocampal theta has been highly correlated to learning and memory processes, the septal modulation of hippocampal function should be considered as an important element in generation and/or retrieval of hippocampal dependent memory. Several aspects need to be considered when studying the septal contribution to hippocampal theta; including the GABA, glutamatergic and cholinergic projections, neuropeptide activity and hyperpolarizing currents in the septum.
Parallel to electrophysiology studies, behavioral studies on medial septum-magnocellular basal forebrain function has been centered in hippocampal-dependent functions such as attention mechanisms and spatial working memory. Recent research reports the contribution of the system to amygdala dependent behaviors, including anxiety, stress, fear and arousal. The challenge as researchers in this field must be to elucidate the mechanism underlying the MS-MBF modulation of such wide variety of brain functions.
On the other hand, clinical relevance of the regions is brought by the fact that loss of cholinergic neurons in MS-MBF in early stages of AD correlates to cognitive impairment In fact, several lines of research on AD pathology study the toxic effects of amyloid-β on septal cholinergic neurons. This region may also be involved in different types of pathology, such as temporal lobe epilepsy. Research in this field, using pilocarpine as an epileptic model, suggests that the interference on cholinergic transmission induces epilepsy. In addition, theta episodes seem to protect hippocampal activity against seizures, but the mechanism underlying this protection has not been completely unraveled.

Finally, although MS-MBF function has been largely studied in relation to hippocampal functions, modulation of cortex and amygdala activity by the MS-MBF should also be considered when studying its global function.
Thus, we encourage researchers to report data covering any of the topics on MS-MBF research regarding its different projections, connectivity patterns and behavioral paradigms in a common chapter to provide a global view of this brain area function.


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