SpikeSSL: A Universal Spike Inference Framework with Dynamics-Informed State-Space Layers

Chenghao Yue, Siming Xing, Shuran Liu, Angran Li, Yuanlong Zhang

Two-photon calcium imaging is a standard tool for recording large neural populations in vivo, yet inferring spikes accurately across the growing diversity of calcium indicators remains an open problem. Existing supervised methods achieve reasonable in-domain accuracy but generalize poorly to unseen indicators, because different indicators induce distinct fluorescence kinetics and signal statistics while existing architectures remain relatively simple generic temporal regressors without dynamics-matched inductive bias. We propose SpikeSSL, a universal spike inference framework whose temporal backbone is a bank of bidirectional IIR state-space layers broadly motivated by calcium dynamics. A multi-modal conditioning encoder maps indicator identity, sampling rate, and trace-level signal statistics into a global conditioning vector that modulates the backbone via Adaptive Layer Normalization, while a heteroscedastic variance head provides calibrated per-frame uncertainty. On a benchmark with five fixed evaluation splits built from 33 public ground-truth datasets, SpikeSSL achieves state-of-the-art performance in both in-domain and zero-shot leave-one-indicator-out settings. We also…