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

Abstract

The lateral septum (LS) is implicated as a hub that regulates a variety of affects, such as reward, feeding, anxiety, fear, sociability, and memory. However, it remains unclear how the LS, previously treated as a structure of homogeneity, exhibits such multifaceted functions. Emerging evidence suggests that different functions of the LS are mediated largely by its diverse input and output connections. It has also become clear that the LS is a heterogeneous region, where its dorsal and ventral poles play dissociable and often opposing roles. This functional heterogeneity can often be explained by distinct dorsal and ventral hippocampal inputs along the LS dorsoventral axis, as well as antagonizing connections between LS subregions. Similarly, outputs from LS subregions to respective downstream targets, such as hypothalamic, preoptic, and tegmental areas, also account for this functional heterogeneity. In this review, we provide an updated perspective on LS subregion classification, connectivity, and functions. We also identify key questions that have yet to be addressed in the field.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 91

1. 1.

   Anthony TE, Dee N, Bernard A, Lerchner W, Heintz N, Anderson DJ (2014 ) Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell 156:522–536.

   Not in our library10.1016/j.cell.2013.12.040

2. 2.

   Azevedo EP, Pomeranz L, Cheng J, Schneeberger M, Vaughan R, Stern SA, Tan B, Doerig K, Greengard P, Friedman JM (2019 ) A role of Drd2 hippocampal neurons in context-dependent food intake. Neuron 102:873–886.e5.

   Not in our library10.1016/j.neuron.2019.03.011

3. 3.

   Azevedo EP, Tan B, Pomeranz LE, Ivan V, Fetcho R, Schneeberger M, Doerig KR, Liston C, Friedman JM, Stern SA (2020 ) A limbic circuit selectively links active escape to food suppression. Elife 9:e58894.

   Not in our library10.7554/elife.58894

4. 4.
   Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway · 2015

   No notice
5. 5.

   Besnard A, Gao Y, TaeWoo Kim M, Twarkowski H, Reed AK, Langberg T, Feng W, Xu X, Saur D, Zweifel LS, Davison I, Sahay A (2019 ) Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses. Nat Neurosci 22:436–446.

   Not in our library10.1038/s41593-018-0330-y

6. 6.

   Besnard A, Miller SM, Sahay A (2020 ) Distinct dorsal and ventral hippocampal CA3 outputs govern contextual fear discrimination. Cell Rep 30:2360–2373.5.

   Not in our library10.1016/j.celrep.2020.01.055

7. 7.

   Brady JV, Nauta WJ (1953 ) Subcortical mechanisms in emotional behavior: affective changes following septal forebrain lesions in the albino rat. J Comp Physiol Psychol 46:339–346.

   Not in our library10.1037/h0059531

8. 8.
   Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context · 2014

   No notice
9. 9.

   Buzsáki G (2015 ) Hippocampal sharp wave-ripple: a cognitive biomarker for episodic memory and planning. Hippocampus 25:1073–1188.

   Not in our library10.1002/hipo.22488

10. 10.

    Calandreau L, Jaffard R, Desmedt A (2007 ) Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning. Learn Mem 14:422–429.

    Not in our library10.1101/lm.531407

11. 11.

    Calandreau L, Desgranges B, Jaffard R, Desmedt A (2010 ) Switching from contextual to tone fear conditioning and vice versa: the key role of the glutamatergic hippocampal-lateral septal neurotransmission. Learn Mem 17:440–443.

    Not in our library10.1101/lm.1859810

12. 12.

    Calderwood MT, Tseng A, Glenn Stanley B (2020 ) Lateral septum mu opioid receptors in stimulation of feeding. Brain Res 1734:146648.

    Not in our library10.1016/j.brainres.2020.146648

13. 13.

    Carus-Cadavieco M, Gorbati M, Ye L, Bender F, van der Veldt S, Kosse C, Börgers C, Lee SY, Ramakrishnan C, Hu Y, Denisova N, Ramm F, Volitaki E, Burdakov D, Deisseroth K, Ponomarenko A, Korotkova T (2017 ) Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking. Nature 542:232–236.

    Not in our library10.1038/nature21066

14. 14.

    Chen YH, Wu JL, Hu NY, Zhuang JP, Li WP, Zhang SR, Li XW, Yang JM, Gao TM (2021 ) Distinct projections from the infralimbic cortex exert opposing effects in modulating anxiety and fear. J Clin Invest 131:e145692.

    Not in our library10.1172/jci145692

15. 15.

    Clemens AM, Wang H, Brecht M (2020 ) The lateral septum mediates kinship behavior in the rat. Nat Commun 11:3161.

    Not in our library10.1038/s41467-020-16489-x

16. 16.

    Dantzer R, Koob GF, Bluthe RM, Le Moal M (1988 ) Septal vasopressin modulates social memory in male rats. Brain Res 457:143–147.

    Not in our library10.1016/0006-8993(88)90066-2

17. 17.

    Davis M (1992 ) The role of the amygdala in fear and anxiety. Annu Rev Neurosci 15:353–375.

    Not in our library10.1146/annurev.ne.15.030192.002033

18. 18.

    De Vries GJ, Buijs RM (1983 ) The origin of the vasopressinergic and oxytocinergic innervation of the rat brain with special reference to the lateral septum. Brain Res 273:307–317.

    Not in our library10.1016/0006-8993(83)90855-7

19. 19.

    Desmedt A, Garcia R, Jaffard R (1999 ) Vasopressin in the lateral septum promotes elemental conditioning to the detriment of contextual fear conditioning in mice. Eur J Neurosci 11:3913–3921.

    Not in our library10.1046/j.1460-9568.1999.00815.x

20. 20.

    Donaldson ZR, Young LJ (2008 ) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322:900–904.

    Not in our library10.1126/science.1158668

21. 21.

    Everts HG, Koolhaas JM (1997 ) Lateral septal vasopressin in rats: role in social and object recognition? Brain Res 760:1–7.

    Not in our library10.1016/s0006-8993(97)00269-2

22. 22.

    Fanselow MS, Dong HW (2010 ) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65:7–19.

    Not in our library10.1016/j.neuron.2009.11.031

23. 23.

    Franklin TR, Druhan JP (2000 ) Expression of Fos-related antigens in the nucleus accumbens and associated regions following exposure to a cocaine-paired environment. Eur J Neurosci 12:2097–2106.

    Not in our library10.1046/j.1460-9568.2000.00071.x

24. 24.

    Fu O, Iwai Y, Narukawa M, Ishikawa AW, Ishii KK, Murata K, Yoshimura Y, Touhara K, Misaka T, Minokoshi Y, Nakajima KI (2019 ) Hypothalamic neuronal circuits regulating hunger-induced taste modification. Nat Commun 10:4560.

    Not in our library10.1038/s41467-019-12478-x

25. 25.

    Harasta AE, Power JM, von Jonquieres G, Karl T, Drucker DJ, Housley GD, Schneider M, Klugmann M (2015 ) Septal glucagon-like peptide 1 receptor expression determines suppression of cocaine-induced behavior. Neuropsychopharmacology 40:1969–1978.

    Not in our library10.1038/npp.2015.47

26. 26.

    Hitti FL, Siegelbaum SA (2014 ) The hippocampal CA2 region is essential for social memory. Nature 508:88–92.

    Not in our library10.1038/nature13028

27. 27.

    Hunsaker MR, Tran GT, Kesner RP (2009 ) A behavioral analysis of the role of CA3 and CA1 subcortical efferents during classical fear conditioning. Behav Neurosci 123:624–630.

    Not in our library10.1037/a0015455

28. 28.

    Janzsó G, Valcz G, Thuma A, Szoke B, Lendvai Z, Abrahám H, Kozicz T, Halasy K (2010 ) Cocaine- and amphetamine-regulated transcript (CART) peptide-immunopositive neuronal elements in the lateral septum: rostrocaudal distribution in the male rat. Brain Res 1362:40–47.

    Not in our library10.1016/j.brainres.2010.09.079

29. 29.

    Jiang JX, Liu H, Huang ZZ, Cui Y, Zhang XQ, Zhang XL, Cui Y, Xin WJ (2018 ) The role of CA3-LS-VTA loop in the formation of conditioned place preference induced by context-associated reward memory for morphine. Addict Biol 23:41–54.

    Not in our library10.1111/adb.12468

30. 30.

    Jonsson S, Morud J, Stomberg R, Ericson M, Söderpalm B (2017 ) Involvement of lateral septum in alcohol’s dopamine-elevating effect in the rat. Addict Biol 22:93–102.

    Not in our library10.1111/adb.12297

31. 31.

    Kask A, Nguyen HP, Pabst R, Von Hörsten S (2001 ) Neuropeptide Y Y1 receptor-mediated anxiolysis in the dorsocaudal lateral septum: functional antagonism of corticotropin-releasing hormone-induced anxiety. Neuroscience 104:799–806.

    Not in our library10.1016/s0306-4522(01)00116-6

32. 32.

    Kelly AM, Ong JY, Witmer RA, Ophir AG (2020 ) Paternal deprivation impairs social behavior putatively via epigenetic modification to lateral septum vasopressin receptor. Sci Adv 6:eabb9116.

    Not in our library10.1126/sciadv.abb9116

33. 33.

    Kosugi K, Yoshida K, Suzuki T, Kobayashi K, Yoshida K, Mimura M, Tanaka KF (2021 ) Activation of ventral CA1 hippocampal neurons projecting to the lateral septum during feeding. Hippocampus 31:294–304.

    Not in our library10.1002/hipo.23289

34. 34.

    Lee EH (1995 ) Corticotropin-releasing factor injected into the lateral septum improves memory function in rats. Chin J Physiol 38:125–129.

    Not in our library

35. 35.

    Leroy F, Park J, Asok A, Brann DH, Meira T, Boyle LM, Buss EW, Kandel ER, Siegelbaum SA (2018 ) A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature 564:213–218.

    Not in our library10.1038/s41586-018-0772-0

36. 36.

    Leutgeb S, Mizumori SJ (2002 ) Context-specific spatial representations by lateral septal cells. Neuroscience 112:655–663.

    Not in our library10.1016/s0306-4522(02)00101-x

37. 37.

    Li YL, Wei S, Liu Q, Gong Q, Zhang QJ, Zheng TG, Yong Z, Chen F, Lawrence AJ, Liang JH (2021 ) Mu-opioid receptors in septum mediate the development of behavioural sensitization to a single morphine exposure in male rats. Addict Biol e13066.

    Not in our library10.1111/adb.13066

38. 38.

    Lin D, Boyle MP, Dollar P, Lee H, Lein ES, Perona P, Anderson DJ (2011 ) Functional identification of an aggression locus in the mouse hypothalamus. Nature 470:221–226.

    Not in our library10.1038/nature09736

39. 39.

    Liu Y, Curtis JT, Wang Z (2001 ) Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster). Behav Neurosci 115:910–919.

    Not in our library10.1037/0735-7044.115.4.910

40. 40.

    Lukas M, Toth I, Veenema AH, Neumann ID (2013 ) Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics. Psychoneuroendocrinology 38:916–926.

    Not in our library10.1016/j.psyneuen.2012.09.018

Cited by papers we hold 1

• Lateral septum-lateral hypothalamus circuit dysfunction in comorbid pain and anxiety · 2023
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.