Abstracts

Rationale: Focal epilepsy is increasingly recognized as a network disorder, wherein epileptiform activity can propagate non-contiguously through the brain via highly interconnected nodes. Our previous study investigated such a network in a mouse model, where interictal spikes (IIS) originating in the primary somatosensory cortex (S1) propagated to ipsilateral (i)M2, contralateral (c)M2, and S1. However, the specific contributions of each node in IIS propagation remained incompletely understood.


Methods: We employed simultaneous Thy-1 and PV-cell mesoscopic calcium imaging to record the initiation and propagation of IISs. To explore the role of different nodes in IIS initiation, we focalized bicuculline injections in S1 and M2, creating distinct IIS foci. Additionally, we investigated the impact of iM2 on IIS propagation by employing Tetrodotoxin (TTx) to selectively inhibit neuronal activity in iM2.


Results: Our findings revealed that S1-originating IIS reverberated throughout the network, with the most robust response observed in iM2. In contrast, M2-originating IIS primarily propagated to cM2 and rarely extended non-contiguously to iS1. Notably, when iM2 was inhibited with TTx, S1-originating IIS could no longer propagate to other nodes.


Conclusions: Our data further support the notion that interictal spikes exploit fiber pathways connecting distributed nodes within the network, and their propagation occurs in a monodirectional manner. Importantly, blocking downstream nodes may effectively halt network-wide IIS propagation.


Funding: N/A