Flexible Cellular Phenotypes Retain a Shared Type-Level Organization across Response Regimes
Year: 2026
Type: article
Abstract: Electrophysiological phenotype is widely used to characterize neuronal identity, but the phenotype measured from a neuron depends on how its intrinsic physiology is probed. Here, we asked which aspects of cellular electrophysiological organization persist across distinct response regimes and how this persistence relates to transcriptomic identity. Using matched Patch-seq measurements from visual cortical GABAergic neurons in male and female mice, we constructed phenotype spaces independently from long-pulse, ramp, and brief-pulse current-clamp responses and compared their organization across the same cells. Cell-level phenotypic relationships were only partially conserved across regimes: cell-cell phenotypic distances were positively correlated across regimes but far from identity, and local neighborhoods reorganized even where global rank structure was partly conserved. Despite this flexibility, the transcriptomic type consistently anchored phenotype beyond coarse Cre-driver identity. At the type level, phenotypic relationships were markedly more conserved across regimes, forming a shared relational backbone with a smaller set of regime-selective rewrites. Transcriptomic distance preferentially tracked this shared type-level structure rather than the magnitude of regime-selective reorganization, and predefined excitability-related gene programs showed the same asymmetry. Together, these results reveal a scale-dependent stability of neuronal phenotype: individual cellular relationships are flexible across probes, whereas type-level biological organization is comparatively stable and more strongly reflected in transcriptomic structure.
Source: eNeuro
Author: Zihan Yang
Institution: Yale University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,925
OpenAlex ID: W7223216829