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PreprintCC BY-NC-NDbioRxiv

Projection populations form a dorsoventral gradient of reward representations in the lateral septum

  1. 1Emory University

Abstract

Several decades ago, the septal region was identified as the most dependable location of intracranial self-stimulation (ICSS) in the brain, but the neural substrates that mediate septal self-stimulation are still unknown. One part of the septal region, the lateral septum (LS), contributes to a number of motivated behaviors and may promote reward-seeking. However, the LS contains different anatomical subregions, complicating the characterization of its reward representations. We examine the responses of LS neurons along its dorsoventral axis using cellular resolution calcium imaging during an operant assay. We find that a greater proportion of neurons are excited in response to sucrose reward in the dorsal LS, while a greater proportion are inhibited in response to sucrose reward in the ventral LS. Additionally, we identify two distinct LS projection populations, one to the nucleus accumbens (NAc) and another to the bed nucleus of the stria terminalis (BNST), which are located in the dorsal and ventral regions of the LS, respectively. These two projection populations also have opposing reward responses and their corresponding optogenetic manipulation supports ICSS. These findings demonstrate how LS projection populations contribute to its functional heterogeneity, especially as it pertains to reward-seeking behavior.

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BibTeX
@misc{isaac2026projection,
  title = {{Projection populations form a dorsoventral gradient of reward representations in the lateral septum}},
  author = {J. Isaac and S. C. Karkare and H. Balasubramanian and V. Olah and M. Rowan and M. Murugan},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.20.760513},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.20.760513v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Projection populations form a dorsoventral gradient of reward representations in the lateral septum
AU  - J. Isaac
AU  - S. C. Karkare
AU  - H. Balasubramanian
AU  - V. Olah
AU  - M. Rowan
AU  - M. Murugan
PY  - 2026
DA  - 2026/10/20
PB  - bioRxiv
DO  - 10.64898/2026.10.20.760513
UR  - https://www.biorxiv.org/content/10.64898/2026.10.20.760513v1
AB  - Several decades ago, the septal region was identified as the most dependable location of intracranial self-stimulation (ICSS) in the brain, but the neural substrates that mediate septal self-stimulation are still unknown. One part of the septal region, the lateral septum (LS), contributes to a number of motivated behaviors and may promote reward-seeking. However, the LS contains different anatomical subregions, complicating the characterization of its reward representations. We examine the responses of LS neurons along its dorsoventral axis using cellular resolution calcium imaging during an operant assay. We find that a greater proportion of neurons are excited in response to sucrose reward in the dorsal LS, while a greater proportion are inhibited in response to sucrose reward in the ventral LS. Additionally, we identify two distinct LS projection populations, one to the nucleus accumbens (NAc) and another to the bed nucleus of the stria terminalis (BNST), which are located in the dorsal and ventral regions of the LS, respectively. These two projection populations also have opposing reward responses and their corresponding optogenetic manipulation supports ICSS. These findings demonstrate how LS projection populations contribute to its functional heterogeneity, especially as it pertains to reward-seeking behavior.
ER  -