Inhibition in the lateral septum increases sucrose intake and decreases anorectic effects of stress

Abstract

Sucrose-overeating rats with decreased anorectic response to stress showed lower stress-induced activation of c-fos expression in the lateral septum (LS). The present study tested a hypothesis that neuronal inhibition in the LS is important for the development and maintenance of the sucrose-overeating phenotype. Sucrose overeating was developed with weekly episodes of food restriction (21 h per day, 4 days per week) followed by 1-h access to sucrose. The anorectic effects of stress on 1-h sucrose intake were estimated using weekly foot shock stress sessions. The development of the sucrose-overeating phenotype was accompanied by a decrease in the anorectic effects of stress and by an increase in LS mRNA expression of a γ-aminobutyric acid (GABA) synthesising enzyme, glutamic acid decarboxylase 67 in stressed rats. Direct recordings of neuronal firing in the LS in rats submitted to repeated weekly cycles of food restriction, sucrose refeeding and stress showed that the development of sucrose overeating increased the percentage of LS neurons inhibited during anticipation and at the start of clusters (CS) of sucrose licking. In addition, the CS-excited LS neurons showed a decrease in responsiveness to sucrose during the development of sucrose overeating. Direct injection of baclofen, an agonist of the GABAB receptor, into the LS decreased the anorectic effects of stress and increased sucrose intake. These results suggest that an increase in inhibitory effects in the LS is important for the development of sucrose overeating and the decreased anorectic effects of stress.

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

“…This activation is likely associated with the increased interaction with food (as reflected in the increased number of bouts in activity-based anorexia rats compared to the ad libitum group) as well as the stimulated food intake during the 1.5-h feeding period. In line with this assumption, key areas of food intake regulation were activated as well, namely the lateral septal nucleus (Mitra et al, 2015), lateral hypothalamic area (Bernardis and Bellinger, 1993), the dorsomedial hypothalamic nucleus and the medial part of the Arc, both expressing the potent orexigenic transmitter neuropeptide Y (Wang et al, 2002; Bi et al, 2012) and lastly also the nucleus of the solitary tract (Stengel and Taché, 2011). Further corroborating the involvement of these nuclei in the orexigenic drive under conditions of activity-based anorexia, a previous study reported a robust upregulation of orexigenic agouti-related peptide and neuropeptide Y, whereas the anorexigenic transmitters pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) were reduced in the Arc of activity-based anorexia rats compared to sedentary food-restricted controls (de Rijke et al, 2005).…”

Hippocampus Contributions to Food Intake Control: Mnemonic, Neuroanatomical, and Endocrine Mechanisms

“…Nucleus accumbens core and shell neurons, other key targets of VTA dopamine signaling, receive substantial innervation from the vSub (86–88). The lateral septum, recently associated with the control of gastric motility (89, 90) and sucrose hyperphagia (91), is another potential feeding-relevant efferent pathway arising from vSub (92, 93) and dorsal CA3 neurons (94). We hypothesize that these monosynaptic outputs from the hippocampus to hypothalamic, striatal, prefrontal cortical, and septal outputs are critical downstream targets for hippocampal neural processing of interoceptive feeding-relevant information.…”

Neural Circuit Mechanisms Underlying Emotional Regulation of Homeostatic Feeding

“…Similar to NAc D1R neurons, synaptic and neural alterations in the septal nucleus are also implicated in emotion-based feeding disorders [36–38]. In particular, inhibition of lateral septum neurons blocked stress-induced reductions in food intake [38], although it remains unclear if septal GABAergic projections to LH GABAergic neurons are involved in the role of lateral septum in stress-induced alterations in feeding, or other components of emotional behavior. However, given that septum both modulates feeding [35, 39–41] and affective behaviors [31], septal inputs to LH appear poised to govern emotional components of feeding behavior.…”