Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

An, Myungmo; Kim, Hyun-Kyung; Park, Ho-Yong; Kim, Kyunghoe; Heo, Gyuryang; Park, Han-Eol; Chung, ChiHye; Kim, Sung-Yon

doi:10.5607/en22024

Cited by 13 publications

(5 citation statements)

References 80 publications

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“…Previous studies have reported that NE enhances excitatory synaptic transmission to LS SST neurons, but does not affect stress-related behaviors. [50] This was consistent with our finding that NE was not required for the LC TH -dLS circuit to alleviate social avoidance following social trauma. We acknowledge that BDNF has been extensively studied in depression, yet there is no consensus in the literature.…”

Section: Discussionsupporting

confidence: 91%

Locus Coeruleus‐Dorsolateral Septum Projections Modulate Depression‐Like Behaviors via BDNF But Not Norepinephrine

Zhang,

Xue,

Wei

et al. 2023

Advanced Science

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Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression‐like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH‐dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression‐like behaviors in both male and female mice. Mechanistically, it is found that brain‐derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant‐like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant‐like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant‐like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant‐like role of the LCTH‐dLSSST pathway in depression via BDNF‐TrkB signaling.

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Section: Discussionsupporting

confidence: 91%

Locus Coeruleus‐Dorsolateral Septum Projections Modulate Depression‐Like Behaviors via BDNF But Not Norepinephrine

Zhang,

Xue,

Wei

et al. 2023

Advanced Science

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“…Notably, Sstexpressing cells (>50% in dorsal LS; >40% in intermediate LS) and Calb1-expressing cells (almost 40% in dorsal LS; almost 30% in intermediate LS) represent most Avpr1a-expressing cells in the LS, suggesting important roles for both subtypes of GABAergic interneurons in V1aR-mediated functions in the LS. Enhanced activity of Sst-expressing neurons in the dorsal LS is associated with increased anxiety-like behaviors (Besnard et al, 2019;An et al, 2022) while suppressed activity of Sst-expressing neurons in the dorsal LS is associated with improved social discrimination behavior (Borie et al, 2021) in mice. Calb1 is almost exclusively expressed in GABAergic neurons in the LS (Zhao et al, 2013), but the function of Calb1-expressing cells in the LS seems unknown.…”

Section: Discussionmentioning

confidence: 99%

Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum

Bredewold

Washington

Veenema

2023

Preprint

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Social play is a highly rewarding behavior that is essential for the development of social skills. Social play is impaired in children diagnosed with autism, a disorder with a strong sex bias in prevalence. We recently showed that the arginine vasopressin (AVP) system in the lateral septum (LS) regulates social play behavior sex-specifically in juvenile rats: Administration of a AVP 1a receptor (V1aR) antagonist increased social play behavior in males and decreased it in females. Here, we demonstrate that glutamate, but not GABA, is involved in the sex-specific regulation of social play by the LS-AVP system. First, males show higher extracellular glutamate concentrations in the LS than females while they show similar extracellular GABA concentrations. This resulted in a baseline sex difference in excitatory/inhibitory balance, which was eliminated by V1aR antagonist administration into the LS: V1aR antagonist increased extracellular glutamate release in females but not in males. Second, administration of the glutamate receptor agonist L-glutamic acid into the LS prevented the V1aR antagonist-induced increase in social play behavior in males while mimicking the V1aR antagonist-induced decrease in social play behavior in females. Third, administration of the glutamate receptor antagonists AP-5 and CNQX into the LS prevented the V1aR antagonist-induced decrease in social play behavior in females. Last, both sexes showed increases in extracellular LS-GABA release upon V1aR antagonist administration into the LS and decreases in social play behavior upon administration of the GABA-A receptor agonist muscimol into the LS, suggesting that GABA is not involved in the sex-specific regulation of social play by the LS-AVP system. Finally, to start identifying the cellular mechanism mediating the sex-specific effects of the LS-AVP system on LS-glutamate, we determined the presence of potential sex differences in the type of LS cells expressing V1aR. However, no sex differences were found in the percentage of Avpr1a+ LS cells expressing markers for either GABAergic neurons, somatostatin-expressing neurons, calbindin 1-expressing neurons, or astrocytes. In conclusion, these findings demonstrate that the LS-AVP system regulates social play sex-specifically via differential local glutamatergic neurotransmission in male and female juvenile rats. Further research is required to uncover the underlying cellular mechanism.

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“…Alternatively, the discrepancy in signal between water, alcohol, and sucrose indicates precise tuning relative to the rewarding properties of these liquids. Because discrete cell types within the LS are tuned to aversive stimuli [44][45][46] , we then assessed LS Pnoc activity in response to footshock and air puff exposure. Footshock elicited a robust increase in LS Pnoc Ca activity in males and females (Fig.…”

Section: Ls Pnoc Respond To Stimuli Associated With Negative Valencementioning

confidence: 99%

“…Indeed, the LS has been implicated in stress and anxiety states, and recent studies leveraging in vivo Ca imaging techniques have revealed heightened activity in genetically defined LS populations during exposure to stimuli associated with negative valence. For example, NTS- 46,57 , SST- 45 , and CRFR2- 44 expressing neurons in the LS are responsive to footshock, and VGAT-expressing neurons are highly responsive to pain 58 . LS Pnoc activity follows this pattern, displaying increased activity during footshock, air puff stimulus, sucrose spray, as well as exploration of the open arm in an EPM.…”

Section: Aud Neurocircuitry: Role For the Lateral Septum In Binge Dri...mentioning

confidence: 99%

Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system

Haun,

Hernandez,

Yan

et al. 2024

Preprint

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High intensity alcohol drinking during binge episodes overwhelmingly contributes to the socioeconomic burden created by Alcohol Use Disorders (AUD). Novel interventions are needed to add to the current therapeutic toolkit and nociceptin receptor (NOP) antagonists have shown promise in reducing heavy drinking days in patients with an AUD. However, an endogenous locus of nociceptin peptide and discrete sites of NOP action underlying this effect remains understudied. Here we show that the lateral septum (LS), a region contributing to binge drinking, is enriched in neurons expressing mRNA coding for the nociceptin peptide (Pnoc). Pnoc-expressing neurons of the LS (LSPnoc) are tuned to stimuli associated with negative valence and display increased excitability during withdrawal from binge-like alcohol drinking. LSPnocactivation was found to have aversive qualities and also potentiates binge-like drinking behavior, suggesting a convergence of circuitry that promotes aversion and drives alcohol consumption. Viral mediated tracing and functional assessment of LSPnocprojection fields revealed GABAergic synapses locally within the LS, and downstream within the lateral hypothalamus (LH) and supramammillary nucleus (SuM). Genetic deletion of NOP from the LS attenuated binge-like alcohol intake in male mice while NOP deletion from the LH and SuM decrease alcohol intake in females. Together, these findings are the first to demonstrate an endogenous population of nociceptin-expressing neurons that contributes to alcohol consumption and identifies sex-dependent modulation of alcohol drinking by NOP.

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Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

Cited by 13 publications

References 80 publications

Locus Coeruleus‐Dorsolateral Septum Projections Modulate Depression‐Like Behaviors via BDNF But Not Norepinephrine

Locus Coeruleus‐Dorsolateral Septum Projections Modulate Depression‐Like Behaviors via BDNF But Not Norepinephrine

Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum

Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system

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