HCN channels enhance synchrony propagation in heterogeneous synfire chains

Abstract

MotivationInformation flow and temporal coding in cortical circuits depend critically on the reliable transmission of precisely timed synchronous spike patterns. Although cortical assemblies achieve such transmission despite pronounced intrinsic heterogeneities and stochastic high-conductance states, the mechanisms underlying effective synchrony propagation under in vivo conditions remain poorly understood. MethodologyIn this study, we address this gap using large-scale, conductance-based models of excitatory and inhibitory neurons organized into feedforward synfire chains operating in noisy, high-conductance regimes. Using independent stochastic search algorithms, we first identified physiologically valid heterogeneous populations of cortical neurons. Both excitatory and inhibitory populations exhibited cellular-scale degeneracy, whereby distinct combinations of biophysically identified molecular components produced signature physiological characteristics. We then constructed synfire chains with varying degrees of heterogeneity using these populations and assessed the propagation of different spike packets across neuronal assemblies. ResultsWe found synchrony propagation to be inherently probabilistic, revealing a stochastic separatrix that separated input patterns that consistently succeeded from those that consistently failed in propagation. The stochastic nature of this separatrix highlighted a critical role for background synaptic fluctuations, defining a regime in which identical inputs alternately propagated or failed across trials solely due to stochastic background activity. Comparing networks with different degrees of intrinsic heterogeneity, we found that increasing heterogeneity did not alter mean propagation efficacy but reduced network-to-network variability, indicating a stabilizing role for intrinsic diversity. Strikingly, when we tested the impact of neuronal intrinsic properties on synchrony propagation, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels emerged as robust enhancers of synchrony propagation across all heterogeneity regimes. Mechanistically, the slow restorative kinetics of HCN conductances narrowed the temporal window for spike initiation, sharpening output synchrony, and improving propagation reliability. This effect was abolished when HCN kinetics were accelerated, underscoring the importance of the slow negative feedback mediated by these channels. ImplicationsTogether, our analyses identify HCN channels as key regulators of synchronous information transfer and reveal strong interactions among intrinsic conductances, input characteristics, neuronal heterogeneity, and stochastic background activity in shaping cortical synchrony propagation. The ability of diverse cellular and network configurations to achieve similar propagation efficacy further highlights degeneracy as a fundamental principle governing robust and flexible neural computation.