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PreprintCC BYbioRxiv

Multimodal profiling and intersectional genetics reveal CA1 border inhibitory neuron diversity and postnatal emergence of retrosplenial connectivity

  • N. Martinez Vizcaino
  • N. Thrupp
  • B. Lorente-Echeverria
  • D. Daaboul
  • M. Alabi
  • C. Milian Alastruey
  • D. Linaro
  • Y. Fourne
  • J. Vandenbempt
  • D. Lukacsovich
  • C. Földy
  • J. Lamote
7 more authors
  • M. Wojno
  • S. Poovathingal
  • M. Fiers
  • K. Wierda
  • L. Lim
  • S. Calafate
  • J. De Wit1
  1. 1VIB-KU Leuven Center for Neuroscience
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Abstract

Inhibitory neurons (INs) at the stratum radiatum/stratum lacunosum-moleculare border of hippocampal CA1 comprise diverse populations, including long-range-projecting neurons that innervate the retrosplenial cortex (RSCtx). However, their molecular organization and developmental connectivity remain poorly understood. Here, we combine multimodal transcriptomic profiling, intersectional genetics, and retrograde tracing to characterize CA1 border INs. We identified two major caudal ganglionic eminence-derived, Cxcl14-enriched populations distinguished by Syt6/Cck-related and Ntng1-expressing transcriptional profiles. We then generated a Cxcl14-Cre mouse line that, when combined with an IN-specific viral enhancer, provides genetic access to CA1 border INs. Retrograde labeling established that CA1 INs projecting to the RSCtx belong to the Ntng1-expressing population, and that this long-range projection emerges during postnatal mouse development, between postnatal days 3 and 5. Finally, analysis of genes encoding cell-surface proteins, key regulators of connectivity, revealed distinct expression profiles in RSCtx-projecting and SYT6-positive INs. Together, these findings establish a molecular and developmental framework for CA1 border IN diversity and provide a genetic strategy for investigating the assembly and function of these inhibitory circuits.

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Cite

BibTeXRIS
BibTeX
@misc{vizcaino2026multimodal,
  title = {{Multimodal profiling and intersectional genetics reveal CA1 border inhibitory neuron diversity and postnatal emergence of retrosplenial connectivity}},
  author = {N. Martinez Vizcaino and N. Thrupp and B. Lorente-Echeverria and D. Daaboul and M. Alabi and C. Milian Alastruey and D. Linaro and Y. Fourne and J. Vandenbempt and D. Lukacsovich and C. Földy and J. Lamote and M. Wojno and S. Poovathingal and M. Fiers and K. Wierda and L. Lim and S. Calafate and J. De Wit},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.29.762784},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762784v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Multimodal profiling and intersectional genetics reveal CA1 border inhibitory neuron diversity and postnatal emergence of retrosplenial connectivity
AU  - N. Martinez Vizcaino
AU  - N. Thrupp
AU  - B. Lorente-Echeverria
AU  - D. Daaboul
AU  - M. Alabi
AU  - C. Milian Alastruey
AU  - D. Linaro
AU  - Y. Fourne
AU  - J. Vandenbempt
AU  - D. Lukacsovich
AU  - C. Földy
AU  - J. Lamote
AU  - M. Wojno
AU  - S. Poovathingal
AU  - M. Fiers
AU  - K. Wierda
AU  - L. Lim
AU  - S. Calafate
AU  - J. De Wit
PY  - 2026
DA  - 2026/10/29
PB  - bioRxiv
DO  - 10.64898/2026.10.29.762784
UR  - https://www.biorxiv.org/content/10.64898/2026.10.29.762784v1
AB  - Inhibitory neurons (INs) at the stratum radiatum/stratum lacunosum-moleculare border of hippocampal CA1 comprise diverse populations, including long-range-projecting neurons that innervate the retrosplenial cortex (RSCtx). However, their molecular organization and developmental connectivity remain poorly understood. Here, we combine multimodal transcriptomic profiling, intersectional genetics, and retrograde tracing to characterize CA1 border INs. We identified two major caudal ganglionic eminence-derived, Cxcl14-enriched populations distinguished by Syt6/Cck-related and Ntng1-expressing transcriptional profiles. We then generated a Cxcl14-Cre mouse line that, when combined with an IN-specific viral enhancer, provides genetic access to CA1 border INs. Retrograde labeling established that CA1 INs projecting to the RSCtx belong to the Ntng1-expressing population, and that this long-range projection emerges during postnatal mouse development, between postnatal days 3 and 5. Finally, analysis of genes encoding cell-surface proteins, key regulators of connectivity, revealed distinct expression profiles in RSCtx-projecting and SYT6-positive INs. Together, these findings establish a molecular and developmental framework for CA1 border IN diversity and provide a genetic strategy for investigating the assembly and function of these inhibitory circuits.
ER  -