New Approaches in Epilepsy Treatment: Fudan University Team Reveals Key Circuit Involved in Piriform Epileptic Seizures and Brain-Wide Functional Reorganization

Release time：2026-02-26 10:14:19

In China, approximately 10 million people suffer from epilepsy. However, the precise and effective treatment of drug-resistant epilepsy remains a major challenge in current medicine. Epilepsy is a brain network dysfunction disease caused by abnormal neuronal discharges, characterized by recurrent seizures. Identifying the “epileptogenic focus” and its key brain networks and circuit mechanisms in the complex brain network is crucial for improving epilepsy treatment.

On February 12, 2026, the research team of Professor Ruiqi Wu from Fudan University’s Institute of Brain Science/Key Laboratory of Brain Function and Brain Diseases published a research paper titled "Piriform seizures mediated by the piriform-entorhino-dentate circuit induce brain-wide functional reorganization in mice" in PLOS Biology (PLoS Biol 24(2): e3003577. doi:10.1371/journal.pbio.3003577). The team established a multi-modal fusion research paradigm centered around Magnetic Resonance Imaging (MRI) (integrating optogenetics, electrophysiology, calcium imaging, and circuit tracing) and, for the first time, revealed the critical role of the piriform cortex (PC) → lateral entorhinal cortex (Lent) → dentate gyrus (DG) neural pathway in driving epileptic seizures and brain-wide functional reorganization. This study provides a theoretical foundation and new ideas for improving epilepsy treatment based on brain network mechanisms.

The research team analyzed MRI data from patients with temporal lobe epilepsy and discovered significant atrophy in the PC area, surpassing traditional focal areas such as the hippocampus and amygdala. Previous studies by the team revealed the cellular mechanisms by which the PC mediates epileptic seizures, showing that activating glutamatergic neurons in the PC or inhibiting GABAergic neurons in the PC could trigger strong systemic seizures in mice and disrupt the brain-wide functional network connectivity (Epilepsia, 2025; doi: 10.1111/epi.18202). In this study, the team used whole-brain fMRI to discover that activating the PC triggers widespread abnormal activation across the entire brain, with the Lent area showing the most persistent and strongest BOLD activation. Resting-state fMRI studies revealed a significant enhancement of functional connectivity between the PC and Lent in the mouse epilepsy model. Viral tracing of neural circuits confirmed that Lent is the main direct target of PC Vglut1+ neurons. Integrating whole-brain functional and projection results allowed precise identification of Lent as a critical node in the brain. Further, through experimental manipulation, the team demonstrated that specifically activating the PC → Lent circuit directly induces seizures, while blocking this circuit eliminated the seizures and brain-wide fMRI abnormalities induced by optogenetic activation of the PC. Additionally, blocking the PC → Lent circuit significantly reduced the fMRI functional connectivity between Lent and DG in the model mice, suggesting that DG is a key secondary downstream brain area mediating seizures. The team also used calcium imaging to show that epileptic activity is transmitted from Lent to DG, capturing the sequential abnormal firing process of PC → Lent → DG with a millisecond delay. Furthermore, inhibiting the Lent → DG circuit also significantly alleviated seizures.

In summary, this study, using ultra-high-field fMRI, successfully constructed a multi-modal research framework and, for the first time, identified a new epileptic pathway — the PC → Lent → DG circuit. This pathway not only initiates epileptic seizures but also drives the spread of seizures throughout the brain, ultimately leading to brain-wide functional reorganization. The research uncovers a novel "input" pathway, distinct from the traditional Papez circuit, providing new potential targets for epilepsy intervention.

Professor Ruiqi Wu’s research team focuses on MRI methods and applies them to brain research: conducting method research on ultra-high-field MRI (with six patent applications and one software copyright, some already industrialized) and integrating MRI with electrophysiology, neural modulation, AI, circuit tracing, and other methods. They investigate brain sensory systems and the mechanisms of neuropsychiatric diseases (with a focus on epilepsy and pain) across multiple scales (brain network, circuits, cells, and molecules) and explore clinical translation strategies. For more information, see the team’s recent related research papers:

Piriform seizures mediated by the piriform-entorhino-dentate circuit induce brain-wide functional reorganization in mice. Plos Biology (2026). https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003577
Asymmetric dynamics of GABAergic system and paradoxical responses of GABAergic neurons in piriform seizures. Epilepsia (2025). https://onlinelibrary.wiley.com/doi/10.1111/epi.18202
fMRI, LFP, and anatomical evidence for hierarchical nociceptive routing pathway between somatosensory and insular cortices. NeuroImage (2024). https://www.sciencedirect.com/science/article/pii/S1053811924000442?via%3Dihub
TMC6 Functions as a GPCR-like Receptor to Sense Noxious Heat Via Gαq Signaling. Cell Discovery (2024). https://www.nature.com/articles/s41421-024-00678-9
Spatial functional reorganizations can serve as potential biomarkers of post facial palsy synkinesis. Cerebral Cortex (2024). https://academic.oup.com/cercor/article/34/5/bhae184/7666599?login=true
Predicting Meningioma Grades and Pathologic Marker Expression via Deep Learning. European Radiology (2024). https://link.springer.com/article/10.1007/s00330-023-10258-2
Differential Recovery of Submodality Touch Neurons and Inter-areal Communication in Sensory Input Deprived Area 3b and S2 Cortices. Journal of Neuroscience (2022). https://www.jneurosci.org/content/42/50/9330.long
Graph Theory Analysis Identified Two Hubs that Connect Sensorimotor and Cognitive and Cortical and Subcortical Nociceptive Networks in the Non-human Primate. NeuroImage (2022). https://www.sciencedirect.com/science/article/pii/S1053811922003688?via%3Dihub

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Chemogenetics	BC-0146	rAAV-EF1α-DIO-hM3Dq-mCherry
Calcium Imaging	BC-0680	rAAV-hSyn-XCaMP-B
Calcium Imaging	BC-0078	rAAV-hSyn-GCaMP6m
Optogenetics	BC-0107	rAAV-EF1α-DIO-hChR2(H134R)-EYFP
Optogenetics	BC-0220	rAAV-hSyn-DIO-ChrimsonR-mCherry
Optogenetics	BC-0597	rAAV-CaMKIIα-ChrimsonR-mCherry
Optogenetics	BC-4643	rAAV-EF1α-FDIO-ChrimsonR-mCherry
Apoptosis	BC-4092	rAAV-hSyn-FDIO-TeLC-P2A-EGFP
Apoptosis	BC-4552	rAAV-EF1α-DIO-TeLC-P2A-EGFP
Apoptosis	BC-0572	rAAV-hSyn-TeLC-P2A-mCherry
Recombinase	BC-0539	rAAV-Retro-hSyn-NLS-Cre-P2A-mCherry
Recombinase	BC-0159	rAAV-Retro-hSyn-Cre
Recombinase	BC-0160	rAAV-Retro-hSyn-Cre-GFP
Fluorescent Proteins	BC-0023	rAAV-Retro-hSyn-mCherry
Fluorescent Proteins	BC-0015	rAAV-EF1α-DIO-EGFP

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New Approaches in Epilepsy Treatment: Fudan University Team Reveals Key Circuit Involved in Piriform Epileptic Seizures and Brain-Wide Functional Reorganization

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New Approaches in Epilepsy Treatment: Fudan University Team Reveals Key Circuit Involved in Piriform Epileptic Seizures and Brain-Wide Functional Reorganization

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