Septal area
Lateral and medial septal nuclei in the septal area of the mouse brain
Details
Identifiers
Latinnuclei septales
MeSHD012686
NeuroNames259
TA98A14.1.09.266
TA25548
FMA61845
Anatomical terms of neuroanatomy

The septal area (medial olfactory area), consisting of the lateral septum and medial septum, is an area in the lower, posterior part of the medial surface of the frontal lobe, and refers to the nearby septum pellucidum.

The septal nuclei are located in this area. The septal nuclei are composed of medium-size neurons which are classified into dorsal, ventral, medial, and caudal groups.[1] The septal nuclei receive reciprocal connections from the olfactory bulb, hippocampus, amygdala, hypothalamus, midbrain, habenula, cingulate gyrus, and thalamus. The septal nuclei are essential in generating the theta rhythm of the hippocampus.

The septal area (medial olfactory area) has no relation to the sense of smell, but it is considered a pleasure zone in animals. The septal nuclei play a role in reward and reinforcement along with the nucleus accumbens. In the 1950s, Olds & Milner showed that rats with electrodes implanted in this area will self-stimulate repeatedly (e.g., press a bar to receive electric current that stimulate the neurons).[2] Experiments on the septal area of humans have taken place since the 1960s.[3][4][5][6]

Connections

Detail of drawing showing components of septal area below corpus callosum.

The septal area is located on the lower posterior part of the frontal lobe. The septal area refers to the nearby septum pellucidum. It is located underneath the corpus callosum and in front of the lamina terminalis. The lamina terminalis is a layer of gray matter that connects the optic chiasma and the anterior commissure.[7] The septal nuclei in the septal area are essential in generating the theta rhythm of the hippocampus.[8]

The dorsal septum projects to the lateral preoptic area, lateral hypothalamus, periventricular hypothalamus and midline thalamus.

Fibers from the ventral half of the septum project topographically to the hippocampal formation, thalamus, hypothalamus and midbrain. Specifically, neurons located along the midline in the vertical limb of the diagonal band of Broca project through the dorsal fornix to all CA fields of the dorsal hippocampus and adjacent subicular cortex. Other fibers from this region project through the stria medullaris to the medial and lateral habenular nuclei, the paratenial and anteromedial nucleus of the thalamus, and through the medial forebrain bundle to the pars posterior of the medial mammillary nucleus.

Cells located in the intermediolateral septum also project through the lateral part of the fimbria to all CA fields of the ventral hippocampus and adjacent subicular and entorhinal cortices. These cells also send fibers through the stria medullaris to the lateral habenular nucleus and mediodorsal thalamic nucleus. Other axons arising from these cells descend through the medial forebrain bundle to terminate in a region dorsal to the interpeduncular nucleus.

The lateral septum is a relay center for connections from the CA3 of the hippocampus to the ventral tegmental area.[9][10] These connections help link reward signals with the context in which they occur.[11][12]

Fibers from the most lateral part of the ventral septum (i.e., bed nucleus of the anterior commissure) project through the stria terminalis to the ventral subiculum.[13] In addition, cells located in the horizontal limb of the diagonal band project massively to the pars posterior of the medial mammillary nucleus, the ventral tegmental area, and amygdala.

Functions of the lateral septum

The lateral septum and movement and reward

The lateral septum is involved in a variety of functions, including emotional, motivational, and spatial behavior. It has been suggested that the LS may regulate interactions between the hippocampus and other regions that mediate goal directed behavior, such as the ventral tegmental area.[14][15] Firing of LS neurons is modulated by both speed and acceleration [16] and spatial location, and that firing is also related to reward and context.[14][17] It has thus been suggested that the lateral septum may incorporate movement into the evaluation of environmental context with respect to motivation and reward.[10]

Lateral septum and social behavior

Inhibitory GABA, and excitatory glutamate, which regulate lateral septum (LS) activity, have been found to be increased during social play in juvenile rats. No sex differences were found in extracellular GABA concentrations during social playing, however, glutamate plays a major role in female social playing. When glutamate receptors are blocked in the LS pharmacologically, there is a significant decrease in female social playing, while males had no decrease in playing. This suggests that in the lateral septum, GABA neurotransmission is involved in social play behavior regulation in both sexes, while glutamate neurotransmission is sex-specific, involved in regulation of social play only in female juvenile rats.[18]

Lateral septum and reproduction

Experiments [19][20] have shown that both testosterone and dihydrotestosterone, when implanted directly into the lateral septum of male rats, caused a significant rise in serum LH and FSH levels, while not significantly increasing serum testosterone and dihydrotestosterone levels respectively. This indicates that the effect is occurring through testosterone receptors and independently of conversion to estrogen via aromatization. As of now, it is unclear, what exact pathway is mediating this phenomenon. Septal lesions significantly decreased serum LH and testosterone levels in male rats, while FSH and prolactin production were unaffected by the surgery. Electrical stimulation of the septum induced the elevation of serum LH and FSH levels.[21] These data suggest that the lateral and/or the medial septum may play a role in the control of GnRH/gonadotropin secretion, and thus, the reproductive axis.

Lateral septum and memory

Despite the diverse direct projection system between the hippocampus and the lateral septum, the first pieces of evidence regarding the role of latter brain area in memory formation and retention have only started to emerge as of 2022. However, recent research has started to shed light on the potentially diverse roles of the lateral septum.

Social memory

The roles of the lateral septum in formation of social memories remain unclear and controversial. It is clear, that some role is being played, as oxytocin and vasopressin, when administered into the lateral septum after social training were able to enhance memory formation,[23][24] while their respective receptor blockers had the opposite effect.[23][25] However, data on effects of pre-training administration of these compounds is mixed, hence the lack of consensus.

Fear memory

Pieces of evidence suggesting the role the lateral septum could be playing in fear memory formation and consolidation have started emerging at the end of the XX. century.[26] Inhibitory avoidance tasks using footshock chambers on mice were deployed to study the effects of the disruption of the lateral septum and hippocampal inputs on fear memory formation and retrieval respectively.[27][28] In both cases, fear memory formation/retrieval was impaired, supporting the hypothesis that hippocampal projections to the lateral septum are at least in part responsible for these mechanisms. The lateral septum could also prove essential in fear memory consolidation. Post-shock adminitration of CRF into the lateral septum enhanced fear memory in the relelvant context;[29] however, this finding still needs to be supported by further studies.

References

  1. ^ St-Amant, Maxime. "Septal nuclei | Radiology Reference Article | Radiopaedia.org". Radiopaedia. Retrieved 23 October 2019.
  2. ^ Olds J, Milner P (1954). "Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain". Journal of Comparative and Physiological Psychology. 47 (6): 419–27. doi:10.1037/h0058775. PMID 13233369. Retrieved 17 March 2013.
  3. ^ Heath RG (1963). "Electrical self-stimulation of the brain in man". The American Journal of Psychiatry. 120 (6): 571–577. doi:10.1176/ajp.120.6.571. ISSN 0002-953X. PMID 14086435.
  4. ^ Moan CE, Heath RG (1972). "Septal stimulation for the initiation of heterosexual behavior in a homosexual male". Journal of Behavior Therapy and Experimental Psychiatry. 3 (1): 23–30. doi:10.1016/0005-7916(72)90029-8. ISSN 0005-7916.
  5. ^ Szalavitz, Maia. "Controversial Surgery for Addiction Burns Away Brain's Pleasure Center". Time. ISSN 0040-781X. Retrieved 4 May 2018.
  6. ^ Zamiska, Nicholas (28 April 2008). "China Bans Irreversible Brain Procedure". Wall Street Journal. ISSN 0099-9660. Retrieved 4 May 2018.
  7. ^ Gaillard, Frank. "Septal area | Radiology Reference Article | Radiopaedia.org". Radiopaedia. Retrieved 21 October 2019.
  8. ^ Butler, T (15 August 2014). "Comparison of human septal nuclei MRI measurements using automated segmentation and a new manual protocol based on histology". NeuroImage. 97: 245–51. doi:10.1016/j.neuroimage.2014.04.026. PMC 4180657. PMID 24736183.
  9. ^ Wirtshafter, Hannah S.; Wilson, Matthew A. (2020-05-26). "Differences in reward biased spatial representations in the lateral septum and hippocampus". eLife. 9: e55252. doi:10.7554/eLife.55252. ISSN 2050-084X. PMC 7274787. PMID 32452763.
  10. ^ a b Wirtshafter, Hannah S.; Wilson, Matthew A. (July 2021). "Lateral septum as a nexus for mood, motivation, and movement". Neuroscience and Biobehavioral Reviews. 126: 544–559. doi:10.1016/j.neubiorev.2021.03.029. ISSN 1873-7528. PMID 33848512. S2CID 233202402.
  11. ^ Wirtshafter HS, Wilson MA (July 2021). "Lateral Septum as a Nexus for Mood, Motivation, and Movement". Neuroscience & Biobehavioral Reviews. 126: 544–559. doi:10.1016/j.neubiorev.2021.03.029. PMID 33848512. S2CID 233202402.
  12. ^ Luo AH, Tahsili-Fahadan P, Wise RA, Lupica CR, Aston-Jones G (14 July 2011). "Linking Context with Reward: A Functional Circuit from Hippocampal CA3 to Ventral Tegmental Area". Science. 333 (6040): 353–357. Bibcode:2011Sci...333..353L. doi:10.1126/science.1204622. PMC 3150711. PMID 21764750.
  13. ^ Risold, P. Y.; Swanson, L. W. (1997-09-19). "Connections of the rat lateral septal complex". Brain Research. Brain Research Reviews. 24 (2–3): 115–195. doi:10.1016/s0165-0173(97)00009-x. PMID 9385454. S2CID 30199261.
  14. ^ a b Wirtshafter, Hannah S.; Wilson, Matthew A. (2020-05-26). "Differences in reward biased spatial representations in the lateral septum and hippocampus". eLife. 9. doi:10.7554/eLife.55252. ISSN 2050-084X. PMC 7274787. PMID 32452763.
  15. ^ Jiang, Jin-Xiang; Liu, Huan; Huang, Zhen-Zhen; Cui, Yue; Zhang, Xue-Qin; Zhang, Xiao-Long; Cui, Yu; Xin, Wen-Jun (January 2018). "The role of CA3-LS-VTA loop in the formation of conditioned place preference induced by context-associated reward memory for morphine: Role of LSc in morphine reward". Addiction Biology. 23 (1): 41–54. doi:10.1111/adb.12468. PMID 27862708. S2CID 2572656.
  16. ^ Wirtshafter, Hannah S.; Wilson, Matthew A. (October 2019). "Locomotor and Hippocampal Processing Converge in the Lateral Septum". Current Biology. 29 (19): 3177–3192.e3. doi:10.1016/j.cub.2019.07.089. PMID 31543450.
  17. ^ Wirtshafter, Hannah S.; Wilson, Matthew A. (2019-10-07). "Locomotor and Hippocampal Processing Converge in the Lateral Septum". Current Biology. 29 (19): 3177–3192.e3. doi:10.1016/j.cub.2019.07.089. ISSN 1879-0445. PMID 31543450.
  18. ^ Bredewold R, Schiavo JK, van der Hart M, Verreij M, Veenema AH (2015). "Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior". Neuroscience. 307: 117–27. doi:10.1016/j.neuroscience.2015.08.052. PMC 4591248. PMID 26318330.
  19. ^ Carreras, Alfonso; Mendoza, Carmen; Ortega, Esperanza; Ruiz, Estrella (1987-07-01). "Testosterone implants into the lateral septum of male rats, a positive effect on LH and FSH secretion". Brain Research Bulletin. 19 (1): 149–151. doi:10.1016/0361-9230(87)90179-1. ISSN 0361-9230. PMID 3115497. S2CID 13489400.
  20. ^ Roca, G. (July 7, 2009). "Crystalline Dihydrotestosterone Implants in the Lateral Septum of Male Rats. A Positive Effect on Lh and FSH". Endocrine Research. 27 (1–2): 35–40. doi:10.1081/ERC-100107167. PMID 11428719. S2CID 38059247. Retrieved December 11, 2022.
  21. ^ Carreras, A.; Robles, R.; Ruiz, E.; Ortega, E.; Mendoza, C.; Osorio, C. (1984-08-01). "Role of the septum on LH, FSH and prolactin secretion in male rats". Brain Research Bulletin. 13 (2): 339–342. doi:10.1016/0361-9230(84)90136-9. ISSN 0361-9230. PMID 6437605. S2CID 8531335.
  22. ^ Rizzi-Wise, Candace A.; Wang, Dong V. (2021-11-01). "Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways". eNeuro. 8 (6). doi:10.1523/ENEURO.0315-21.2021. ISSN 2373-2822. PMC 8647703. PMID 34764187.
  23. ^ a b Dantzer, Robert; Koob, George F.; Bluthe´, Rose-Marie; Le Moal, Michel (1988-08-02). "Septal vasopressin modulates social memory in male rats". Brain Research. 457 (1): 143–147. doi:10.1016/0006-8993(88)90066-2. ISSN 0006-8993. PMID 3167559. S2CID 32037924.
  24. ^ P. Popik 1, P.E. Vos, J.M. Van Ree Behav Pharmacol 1992 Aug;3(4):351-358. Neurohypophyseal hormone receptors in the septum are implicated in social recognition in the rat PMID 11224137
  25. ^ Lukas, Michael; Toth, Iulia; Veenema, Alexa H.; Neumann, Inga D. (2013-06-01). "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 (6): 916–926. doi:10.1016/j.psyneuen.2012.09.018. ISSN 0306-4530. PMID 23102690. S2CID 43827714.
  26. ^ Desmedt, Aline; Garcia, René; Jaffard, Robert (1999-11). "Vasopressin in the lateral septum promotes elemental conditioning to the detriment of contextual fear conditioning in mice: Vasopressin in the LS promotes elemental conditioning". European Journal of Neuroscience. 11 (11): 3913–3921. doi:10.1046/j.1460-9568.1999.00815.x.
  27. ^ Opalka, Ashley N.; Wang, Dong V. (2020-08-01). "Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition". Learning & Memory. 27 (8): 310–318. doi:10.1101/lm.051797.120. ISSN 1072-0502. PMC 7365017. PMID 32669386.
  28. ^ Besnard, Antoine; Gao, Yuan; TaeWoo Kim, Michael; Twarkowski, Hannah; Reed, Alexander Keith; Langberg, Tomer; Feng, Wendy; Xu, Xiangmin; Saur, Dieter; Zweifel, Larry S.; Davison, Ian; Sahay, Amar (2019). "Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses". Nature Neuroscience. 22 (3): 436–446. doi:10.1038/s41593-018-0330-y. ISSN 1097-6256. PMC 6387640. PMID 30718902.
  29. ^ E H Lee (1995) Chin J Physiol Corticotropin-releasing factor injected into the lateral septum improves memory function in rats 1995;38(3):200 PMID 8697897

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