The laboratory has pioneered investigations into the role of medial septum in chronic pain. Our postulate is that the medial septum is a nodal region that modulates network mechanisms in the CNS which underpin the altered perception (i.e., hypersensitivity) and spontaneous pain. In context of foregoing, we have observed, for example, that non-cholinergic, especially GABAergic neurons in the region modulate pain-induced aversion suggesting that these neurons have a potential to play a crucial role in sustaining the aversive-fearful state of chronic pain. The effect of GABAergic neurons was related to modulation of affect related cell signalling in medial prefrontal cortex and contextual learning in hippocampus. However, interestingly, the GABAergic neurons did not influence acute pain behaviours.

On the other hand, we found that manipulating septal cholinergic neurons modulated acute pain behaviours and peripheral hypersensitivity. Surprisingly, we observed that the medial septum can switch role in a pain-state-dependent fashion such that stimulating septal neurons evoked analgesia against background of chronic pain, while same stimuli in naive animals evoked pain.

The medial septum is also implicated in depression, while its role in learning and memory has been well explored. Using a variety of techniques - such as electrophysiology, optogenetics, in vivo imaging, and molecular and cellular techniques - we have taken a system neurobiology approach to understand the circuit mechanisms and molecular events in medial septum that influence chronic pain, mood and learning and memory. Particularly, we ae interested to know if mechanisms underlying pain, mood and learning and memory intersect and how they change with age. Such an approach may inform translation to humans.