This work would not have been possible without the commitment, work, and enthusiasm of a truly diverse team starting from Ryder Gwinn, Rebeca de Frates, Anirban Nandi, and Rusty Mann.
Importantly, we found that the three conductances shaping
#singlecell responses also drove higher
#excitability in a
#human-like
#brain-circuit, as observed in human patients with late-stage
#temporal #lobe #epilepsy.
We used
#parallelcomputing and
#biophysical #simulations to go from deep,
#multimodal #feature changes to
#causal #differences. Result? Three conductances explained
#phenotypic,
#disease-related changes, an observation supported by subsequent
#snRNA analysis.
Long story short: we found that disease progression gave rise to changes across all
#modalities. What are the
#underlying #causes of these cellular phenotypic changes and how are they manifested at the
#brain #circuit-level, for example in the form of
#seizures?
We decided to focus our study on a single
#celltype, dentate gyrus granule cells, and produce multiple
#singlecell #data #modalities:
#snRNA,
#ephys, reconstructed morphologies and synaptic density.
Back in 2016, together with Jonathan Ting we thought looking at
#singlecells in the living, resected hippocampal tissue excised from
#epilepsy #patients was such a unique opportunity to study the
#disease and, ultimately, make a
#difference in the lives of
#patients.
Our paper spearheaded by the amazing Anatoly Buchin is finally published !
https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01769-7