H-current modulation of cortical Up and Down states

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 are generated not only during slow wave sleep and deep anaesthesia, but also in association with disorders of consciousness and brain lesions. 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 fivefold reduction in oscillation frequency. In a biophysical recurrent network model, we identified the cellular mechanisms underlying this transformation of network dynamics: an increased neuronal input resistance and membrane time constant, increasing neuronal responsiveness to even weak inputs. A partial block of h-current therefore resulted in a change in brain state. HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, which generate h-current, are known targets for neuromodulation, suggesting potential pathways for dynamic control of brain rhythms. KEY POINTS: We investigated the role of h-current in shaping emergent cortical slow oscillation dynamics, specifically Up and Down states, in cortical slices. Blocking h-current transformed Up states into prolonged plateaus of sustained firing, lasting up to 4 s. Down states were also significantly elongated and the oscillatory frequency decreased. A biophysical model of the cortical network replicated these findings and allowed us to explore the underlying mechanisms. An increase in cellular input resistance and time constant led to a rise in network excitability, synaptic responsiveness and firing rates. Our results highlight the significant role of h-current in controlling cortical slow rhythmic patterns, making it a relevant target for neuromodulators regulating brain states.