H-current modulation of cortical Up and Down states

Abstract Understanding the link between cellular processes and brain function remains a key challenge in neuroscience. One crucial aspect is the interplay between specific ion channels and network dynamics. This work reveals a role for h-current, a hyperpolarization-activated cationic current, in shaping cortical slow oscillations. Cortical slow oscillations exhibit rhythmic periods of activity (Up states) alternating with silent periods (Down states). By progressively reducing h-current in both cortical slices and in a computational model, we observed Up states transformed into prolonged plateaus of sustained firing, while Down states were also significantly extended. This transformation led to a five-fold reduction in oscillation frequency. In a biophysical recurrent network model, we identified the cellular mechanisms: an increased input resistance and membrane time constant, increasing neuronal responsiveness to even weak inputs. HCN channels, the molecular basis of h-current, are known neuromodulatory targets, suggesting potential pathways for dynamic control of brain rhythms.