The Lateral Septum and the Regulation of Anxiety

Abstract

Compared to other structures, such as the amygdala, the lateral septum’s (LS) role in the regulation of anxiety and/or behavioural defense is relatively understudied. Thus, the overarching goal of this thesis was to further investigate its contribution to rats’ anxiety-related behaviours. In Chapter 2, we demonstrate, for the first time, that while the dorsal LS does not mediate rats’ appetitive motivation or anxiety in the novelty induced suppression of feeding (NISF) paradigm, it does modulate their defensive behaviours in the elevated plus maze (EPM) and shock probe burying tests (SPBT). In Chapter 3, we are the first to show that bilateral infusions of histamine, a neurochemical previously linked to anxiety, into the LS reduce rats’ anxiety-related behaviours in the EPM and NISF. In addition, we report a novel double dissociation between lateral septal H1 and H2, and H3 receptors in their regulation of rats’ defensive behaviours in those two paradigms. More specifically, the H1 and H2 receptors contribute to rats’ hyponeophagia in the NISF but not their open arm exploration in the EPM, while the H3 receptors modulate rats’ defensive behaviors in the EPM but not in the NISF. Finally, in Chapter 4, we report for the first time that infusions of histamine into the LS, which produce behavioural anxiolysis, increase rather than decrease the frequency of reticular-elicited hippocampal theta activity, a putative neurophysiological correlate of anxiolytic-drug action. Altogether, the data in this thesis increase our understanding of how the LS contributes to rats’ defensive behaviours and adds to the existing literature regarding the neurobiology of fear/anxiety. More importantly though, the data presented here could ultimately aid in the development of novel drugs to treat anxiety disorders in humans.