Medial septum neurokinin- and somatostatin-sensitive mechanisms mediate sensorimotor and nociceptive behaviours

Abstract

The forebrain medial septum (MS), implicated in affective-motivational behaviours, is enriched in substance P (SP) sensitive neurokinin-1 receptors (NK1R) and somatostatin (SST) receptors (SSTR) that are located almost exclusively on cholinergic and GABAergic neurons, respectively. However, the physiological function of these receptors is poorly understood. This study characterized the actions of intraseptal SP on electrophysiological indices of septo-hippocampal activation, then utilised NK1 receptor antagonist, L-733,060, and SST to investigate the physiological role of endogenous neurotransmission at NK1R, and SST-sensitive mechanisms, in novel open field and formalin test of inflammatory pain. The findings showed that neurotransmission at NK1R mediates formalin-induced electrophysiological responses in the septo-hippocampus in anaesthetized and behaving animals. Furthermore, parallel NK1R- and SST-sensitive mechanisms affect different aspects of animal behaviours in both tests, collectively modulating attention and habituation in open field and driving formalin-induced nociception. This brings out a newer peptidergic dimension of septal physiology in nociception.

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

“…Alongside muscimol and lidocaine, a wide variety of other manipulation approaches have also been studied in relation to MSDB and locomotion. For example, infusion of histamine or pyrilamine increased locomotion (Zarrindast et al, 2006), depletion of the relaxin-family peptide-3 receptor (RXFP3) impaired spatial strategy search (Haidar et al, 2019), the neurokinin 1 receptor (NK1R) facilitated exploratory behaviour (Ng et al, 2020), while CaV3.1 (T-type voltage gated calcium channel) knock down increased exploration of an object (Jung et al, 2019). Moreover, MK 801 and ketamine lead to hyperlocomotion (Ma and Leung, 2007), while a somatostatinsensitive mechanism facilitated inactivity periods in open field (Ng et al, 2020).…”

“…For example, infusion of histamine or pyrilamine increased locomotion (Zarrindast et al, 2006), depletion of the relaxin-family peptide-3 receptor (RXFP3) impaired spatial strategy search (Haidar et al, 2019), the neurokinin 1 receptor (NK1R) facilitated exploratory behaviour (Ng et al, 2020), while CaV3.1 (T-type voltage gated calcium channel) knock down increased exploration of an object (Jung et al, 2019). Moreover, MK 801 and ketamine lead to hyperlocomotion (Ma and Leung, 2007), while a somatostatinsensitive mechanism facilitated inactivity periods in open field (Ng et al, 2020). A recent study applied the cooling of MSDB as an alternative and complementary tool to pharmacology in order to investigate the overall effect of the MSDB circuit inhibition.…”