Differential and complementary roles of medial and lateral septum in the orchestration of limbic oscillations and signal integration.

Anatomical differences between the medial and lateral septum have associated these nuclei with dissimilar functional roles and behaviours. While the medial septum has been implicated, predominantly, in theta rhythm generation along the septo-hippocampal axis, the lateral septum has mainly been investigated in the context of septo-hypothalamic dialogue. Recent advances suggest that medial and lateral septum are more closely functionally related than previously appreciated. Here, we explore the hypothesis that the medial septum mediates ascending septo-hippocampal theta propagation, while the lateral septum processes a descending hippocampo-septal and septo-hypothalamic reinforcement signal that mediates navigation during motivated behaviour. The generation and propagation of theta rhythm are critical for the initiation of exploratory behaviour. Indeed, theta signal processing of medial and lateral septum nuclei may well be involved in the integration of spatial, rewarding and locomotor signals across different brain networks. We review here the structural features, anatomical connectivity and functional properties of the medial and lateral septum. We discuss the heterogeneous anatomy of the lateral septum, which is composed of diverse subregions with distinct ascending and descending projections, and we relate the physiological characteristics of septal nuclei to their functional relationships with the hippocampal formation, the hypothalamus and the brainstem reticular formation during motivated spatial navigation.