A robust low-dimensional manifold organizes neuronal responses to sustained input

Abstract

Neuronal electrophysiological identity is expressed through responses to input, but how this identity is organized across distinct physiological input regimes remains unclear. Conventional descriptors such as firing rate, threshold, latency, or response amplitude capture local aspects of excitability, while different current-clamp protocols expose different dimensions of cellular response. Here, we asked whether protocol-specific response measurements reveal distinct physiological axes while preserving shared organization among genetically targeted cell groups. Using intracellular current-clamp recordings from mouse visual cortex, we constructed multivariate response geometries from long-pulse, ramp, and brief-pulse stimulation protocols, respectively probing sustained spiking output, dynamic recruitment, and fast transient response/gain. Each protocol revealed a structured and interpretable geometry: long-pulse responses organized cells along sustained-output and high-current response dimensions, ramp responses isolated recruitment-threshold structure, and brief-pulse responses captured fast transient response and gain-related variation. Driver-defined groups occupied ordered positions within these geometries, indicating that protocol-specific response axes were linked to cell-group organization. Across protocols, driver-defined group distance structures remained positively aligned after balanced resampling and comparison with driver-label shuffle null models, showing that protocol-specific geometries retained partially shared relational structure. These findings support a protocol-resolved view of cellular electrophysiological identity as a multidimensional response organization, in which distinct physiological probes reveal protocol-specific response modes embedded within shared cell-group structure.