PUBLICATION
Maximally selective single-cell target for circuit control in epilepsy models
- Authors
- Hadjiabadi, D., Lovett-Barron, M., Raikov, I.G., Sparks, F.T., Liao, Z., Baraban, S.C., Leskovec, J., Losonczy, A., Deisseroth, K., Soltesz, I.
- ID
- ZDB-PUB-210702-12
- Date
- 2021
- Source
- Neuron 109(16): 2556-2572.e6 (Journal)
- Registered Authors
- Baraban, Scott
- Keywords
- adult-born granule cells, calcium imaging, effective connectivity modeling, epilepsy, higher-order organization, hubs, motifs, network science, seizure control, single-cells
- MeSH Terms
-
- Animals
- Cell Communication/physiology*
- Dentate Gyrus/pathology
- Dentate Gyrus/physiopathology
- Epilepsy/physiopathology*
- Nerve Net/physiopathology
- Neurons/physiology*
- Seizures/physiopathology*
- Zebrafish
- PubMed
- 34197732 Full text @ Neuron
Citation
Hadjiabadi, D., Lovett-Barron, M., Raikov, I.G., Sparks, F.T., Liao, Z., Baraban, S.C., Leskovec, J., Losonczy, A., Deisseroth, K., Soltesz, I. (2021) Maximally selective single-cell target for circuit control in epilepsy models. Neuron. 109(16):2556-2572.e6.
Abstract
Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging of larval zebrafish and chronically epileptic mice, biologically constrained effective connectivity modeling, and higher-order motif-focused network analysis. We uncovered a novel functional cell type that preferentially emerged in the preseizure state, the superhub, that was unusually richly connected to the rest of the network through feedforward motifs, critically enhancing downstream excitation. Perturbation simulations indicated that disconnecting superhubs was significantly more effective in stabilizing epileptic circuits than disconnecting hub cells that were defined traditionally by connection count. In the dentate gyrus of chronically epileptic mice, superhubs were predominately modeled adult-born granule cells. Collectively, these results predict a new maximally selective and minimally invasive cellular target for seizure control.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping