Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

Rizzi-Wise, Candace A.; Wang, Dong V.

doi:10.1523/eneuro.0315-21.2021

Cited by 70 publications

(75 citation statements)

References 92 publications

(200 reference statements)

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“…The LS is implicated in several social behaviors and plays a critical role in how animals assess and respond to social contexts (Sheehan et al, 2004 ). The LS acts as a gating mechanism to control several emotion regulation processes, such as reward, anxiety, sociability, and memory (Sheehan et al, 2004 ; Rizzi-Wise and Wang, 2021 ). Among these behaviors, the LS is particularly important for social approach.…”

Section: Discussionmentioning

confidence: 99%

Synergistic consequences of early-life social isolation and chronic stress impact coping and neural mechanisms underlying male prairie vole susceptibility and resilience

Sailer

Patel

Park

et al. 2022

Front. Behav. Neurosci.

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Chronic stress can be challenging, lead to maladaptive coping strategies, and cause negative mental and physical health outcomes. Early-life adversity exposes developing young to physical or psychological experiences that risks surpassing their capacity to effectively cope, thereby impacting their lifetime physical and mental wellbeing. Sensitivity to stressful events, like social isolation, has the potential to magnify stress-coping. Chronic stress through social defeat is an established paradigm that models adverse early-life experiences and can trigger enduring alterations in behavioral and neural phenotypes. To assess the degree to which stress resilience and sensitivity stemming from early-life chronic stress impact sociability, we exposed male prairie voles to chronic social defeat stress (CSDS) during adolescence. We simultaneously exposed subjects to either social isolation (CSDS+Isol) or group housing (CSDS+Soc) during this crucial time of development. On PND41, all subjects underwent a social approach test to examine the immediate impact of isolation, CSDS, or their combined effects on sociability. Unlike the CSDS+Isol group which primarily displayed social avoidance, the CSDS+Soc group was split by individuals exhibiting susceptible or resilient stress phenotypes. Notably, the Control+Soc and CSDS+Soc animals and their cage-mates significantly gained body weight between PND31 and PND40, whereas the Control+Isol and CSDS+Isol animals did not. These results suggest that the effects of early-life stress may be mitigated by having access to social support. Vasopressin, oxytocin, and opioids and their receptors (avpr1a, oxtr, oprk1, oprm1, and oprd1) are known to modulate social and stress-coping behaviors in the lateral septum (LS). Therefore, we did an mRNA expression analysis with RT-qPCR of the avpr1a, oxtr, oprk1, oprm1, and oprd1 genes to show that isolation and CSDS, or their collective influence, can potentially differentially bias sensitivity of the LS to early-life stressors. Collectively, our study supports the impact and dimensionality of early-life adversity because the type (isolation vs. CSDS), duration (acute vs. chronic), and combination (isolation + CSDS) of stressors can dynamically alter behavioral and neural outcomes.

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Section: Discussionmentioning

confidence: 99%

Synergistic consequences of early-life social isolation and chronic stress impact coping and neural mechanisms underlying male prairie vole susceptibility and resilience

Sailer

Patel

Park

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

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“…The core nodes for controls are putative homologs of the pre-optic area (PM, Ppa l ) and the lateral septum (Vv a ) in mammals (O’Connell and Hofmann, 2011 ) suggesting activity in the SDMN in the absence of social stimuli that engages salience monitoring in the environment, through the lateral septum (Rizzi-Wise and Wang, 2021 ) linked to the regulation of internal states, through the pre-optic area.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Aggression Are Paralleled by Differential Activation of the Brain Social Decision-Making Network in Zebrafish

Scaia

Akinrinade

Petri

et al. 2022

Front. Behav. Neurosci.

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Although aggression is more prevalent in males, females also express aggressive behaviors and in specific ecological contexts females can be more aggressive than males. The aim of this work is to assess sex differences in aggression and to characterize the patterns of neuronal activation of the social-decision making network (SDMN) in response to intra-sexual aggression in both male and female zebrafish. Adult fish were exposed to social interaction with a same-sex opponent and all behavioral displays, latency, and time of resolution were quantified. After conflict resolution, brains were sampled and sex differences on functional connectivity throughout the SDMN were assessed by immunofluorescence of the neuronal activation marker pS6. Results suggest that both sexes share a similar level of motivation for aggression, but female encounters show shorter conflict resolution and a preferential use of antiparallel displays instead of overt aggression, showing a reduction of putative maladaptive effects. Although there are no sex differences in the neuronal activation in any individual brain area from the SDMN, agonistic interactions increased neuronal activity in most brain areas in both sexes. Functional connectivity was assessed using bootstrapped adjacency matrices that capture the co-activation of the SDMN nodes. Male winners increased the overall excitation and showed no changes in inhibition across the SDMN, whereas female winners and both male and female losers showed a decrease in both excitation and inhibition of the SDMN in comparison to non-interacting control fish. Moreover, network centrality analysis revealed both shared hubs, as well as sex-specific hubs, between the sexes for each social condition in the SDMN. In summary, a distinct neural activation pattern associated with social experience during fights was found for each sex, suggesting a sex-specific differential activation of the social brain as a consequence of social experience. Overall, our study adds insights into sex differences in agonistic behavior and on the neuronal architecture of intrasexual aggression in zebrafish.

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“…Although no circuit involving the LS has yet been identified that exerts this inhibitory effect on this pathway, this does not exclude this as a possibility. This is particularly since emerging evidence suggests that LS may be divided into functionally distinct subregions (see Rizzi‐Wise & Wang, 2021 for a review) and multiple regions may feed into this and other similar circuits.…”

Section: Discussionmentioning

confidence: 99%

The role of the lateral septum in neuropsychiatric disease

Patel

2022

J of Neuroscience Research

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The lateral septum (LS) is a structure in the midline of the brain that is interconnected with areas associated with stress and feeding. This review highlights the role of the LS in anxiety, depression, and eating disorders and their comorbidity. There is a prevailing view that the LS is anxiolytic. This review finds that the LS is both anxiolytic and anxiogenic. Furthermore, the LS can promote and inhibit feeding. Given these shared roles, the LS represents a common site for the comorbidity of neuropsychiatric disorders, and therefore a potential pharmacological target. This is crucial since currently available treatments are not always effective. Corticotrophin-releasing factor 2 antagonists are potential drugs for the treatment of anxiety and anorexia and require further research. Furthermore, other drugs currently in trials for binge eating, such as alpha-adrenergic agonists, may in fact promote food intake. It is hoped that the advancements in chemo-and optogenetic techniques will allow future studies to profile the specific neural connections of the LS and their function. This information could facilitate our understanding of the underlying mechanisms, and therefore pharmacological targets, of these psychiatric conditions.

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Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

Cited by 70 publications

References 92 publications

Synergistic consequences of early-life social isolation and chronic stress impact coping and neural mechanisms underlying male prairie vole susceptibility and resilience

Synergistic consequences of early-life social isolation and chronic stress impact coping and neural mechanisms underlying male prairie vole susceptibility and resilience

Sex Differences in Aggression Are Paralleled by Differential Activation of the Brain Social Decision-Making Network in Zebrafish

The role of the lateral septum in neuropsychiatric disease

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