The Medial Septum as a Smart Clock: New Aspects of its Function Beyond Pacemaking

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Background

The role of the medial septum as the main clock of theta rhythm, the dominant oscillation of the limbic system during information collecting behaviors and REM sleep, is supported by several lines of research. Single-cell recording and labeling techniques, later complemented by optogenetic methods enabled the identification of the core circuit of the medial septal rhythm generator composed of mainly interconnected GABAergic (mainly parvalbumin-expressing) neurons. Recent research has identified the still largely unexplored glutamatergic neuron group as a key node that controls both movement speed and theta. Finally, the modulatory role shaping theta and heterogeneity of the third major medial septal neuron type, the cholinergic cells were revealed in the past few years. Neuron type-selective manipulations provided unequivocal evidence of the indispensability of the medial septum in memory processes. Accordingly, deterioration of memory functions in dementia is often linked to the disruption of the basal forebrain circuit of which the medial septum is a central part.

Despite decades of research, the medial septum is still an enigmatic brain region. Besides the growing number of studies investigating the medial septum from a theta-centric perspective, there is a relative scarcity of information related to its probable and more direct participation in any coding process, for example, whether medial septal population activity carries information about behavioral events read out by downstream regions. Its multicomponent reciprocal connection with the hippocampus puts it in a key position for controlling hippocampus-dependent memory processes. In this Research Topic, we aim to compile a collection of papers that both deepen our knowledge about the known role of the medial septum in synchronizing components of the episodic memory circuit and unravel unknown facets of the medial septal function. Subtopics of interest include:

• Novel information on less known neuron types (especially the glutamatergic and non-Parvalbumin GABAergic neurons).

• Role of the medial septum in the modulation of oscillations other than theta.

• Integration of information from various brain subsystems converging on the pacemaker circuit and how it modulates the theta rhythmic output.

• Newly identified functions of the medial septum beyond rhythm generation i.e. what kind of codes do medial septal neurons carry (e.g. speed)?

• Novel findings on basal forebrain pathologies in neuropsychiatric diseases.

• New models of medial septum function.


We would like to thank Dr. Peter C Petersen for their contribution to the development of this article collection.

Keywords: Theta rhythm, Memory, Navigation, Synchronization, Cholinergic

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