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Peer-reviewedCC BY-NCCerebral cortex (New York, N.Y. : 1991)

GABAergic subiculum-medial entorhinal projection in mice and rats.

4 affiliations
  1. 1Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.
  2. 2Laboratory of Systems Neuroscience, Tohoku University Graduate School of Life Sciences, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
  3. 3Division for the Establishment of Frontier Sciences of the Organization for Advanced Studies, Tohoku University, Sendai 980-8577, Japan.
  4. 4Komaba Institute for Science, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.

Abstract

The subiculum (SUB) is a major hippocampal output hub that routes information to cortical and subcortical targets, and its long-range projections are considered excitatory. Using enhancer-driven adeno-associated viral vectors to selectively label γ-aminobutyric acid (GABA)-releasing neurons across species, here we show that the dorsal SUB also sends an inhibitory projection to the dorsal part of the medial entorhinal cortex (MEC) in mice and rats. Anterograde tracing in mice revealed that the dorsal SUB contains GABAergic neurons that project sparsely to all layers of the dorsal MEC with enrichment in superficial layers, in contrast to the glutamatergic SUB axons targeting MEC layer V. Slice electrophysiology demonstrated that these GABAergic axons form inhibitory synapses in the MEC. A subset of projecting neurons expressed parvalbumin (PV), whereas somatostatin-positive neurons were infrequent. Consistently, PV neuron-specific anterograde tracing recapitulated the SUB-to-MEC projection. In rats, subicular GABAergic axons were enriched in MEC layer II, and SynaptoTAG2-labeled presynaptic boutons were positive for the vesicular GABA transporter, supporting inhibitory synapse formation. Anterograde tracing of PV neurons similarly recapitulated the laminar axonal distribution in the MEC. These results identify a conserved PV-associated inhibitory SUB-to-MEC projection with specific laminar organization, extending the canonical excitatory view of subicular output.

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BibTeX
@article{aimi2026gabaergic,
  title = {{GABAergic subiculum-medial entorhinal projection in mice and rats.}},
  author = {Takahiro Aimi and Takumi Shibuya and Haruka Umeno and Keiko Karasawa and Ken-Ichiro Tsutsui and Shinya Ohara and Takuma Kitanishi},
  journal = {Cerebral cortex (New York, N.Y. : 1991)},
  year = {2026},
  month = oct,
  doi = {10.1093/cercor/bhag177},
  url = {https://europepmc.org/article/MED/42910933},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - GABAergic subiculum-medial entorhinal projection in mice and rats.
AU  - Takahiro Aimi
AU  - Takumi Shibuya
AU  - Haruka Umeno
AU  - Keiko Karasawa
AU  - Ken-Ichiro Tsutsui
AU  - Shinya Ohara
AU  - Takuma Kitanishi
PY  - 2026
DA  - 2026/10/01
JO  - Cerebral cortex (New York, N.Y. : 1991)
DO  - 10.1093/cercor/bhag177
UR  - https://europepmc.org/article/MED/42910933
AB  - The subiculum (SUB) is a major hippocampal output hub that routes information to cortical and subcortical targets, and its long-range projections are considered excitatory. Using enhancer-driven adeno-associated viral vectors to selectively label γ-aminobutyric acid (GABA)-releasing neurons across species, here we show that the dorsal SUB also sends an inhibitory projection to the dorsal part of the medial entorhinal cortex (MEC) in mice and rats. Anterograde tracing in mice revealed that the dorsal SUB contains GABAergic neurons that project sparsely to all layers of the dorsal MEC with enrichment in superficial layers, in contrast to the glutamatergic SUB axons targeting MEC layer V. Slice electrophysiology demonstrated that these GABAergic axons form inhibitory synapses in the MEC. A subset of projecting neurons expressed parvalbumin (PV), whereas somatostatin-positive neurons were infrequent. Consistently, PV neuron-specific anterograde tracing recapitulated the SUB-to-MEC projection. In rats, subicular GABAergic axons were enriched in MEC layer II, and SynaptoTAG2-labeled presynaptic boutons were positive for the vesicular GABA transporter, supporting inhibitory synapse formation. Anterograde tracing of PV neurons similarly recapitulated the laminar axonal distribution in the MEC. These results identify a conserved PV-associated inhibitory SUB-to-MEC projection with specific laminar organization, extending the canonical excitatory view of subicular output.
SN  - 1047-3211
SN  - 1460-2199
ER  -