HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species

Radaelli, C.; Schmitz, M.; Liu, X.-P.; Sawchuk, S.; Opitz-Araya, X.; Hudson, M.; Taskin, N.; Bertagnolli, D.; Goldy, J.; Ko, A. L.; Grannan, B. L.; Hauptman, J. S.; Patel, A. P.; Cobbs, C.; Smith, K. A.; Spain, W. J.; Lein, E. S.; Bakken, T.; Dembrow, N. C.; Ting, J. T.; Kalmbach, B. E.

doi:10.1101/2025.08.22.671856

Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.08.22.671856

HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species

View original source ↗Export metadata ↓

Abstract

The physiological properties of human and rodent neurons differ, yet the extent to which these differences reflect human specializations is often unclear. Compared with their rodent counterparts, human supragranular pyramidal neurons possess enriched HCN-channel-dependent intrinsic membrane properties and a related sensitivity to synaptic inputs containing delta/theta band frequencies. We tested whether other primate species possess enriched HCN-channel dependent membrane properties. We found ubiquitous HCN1 subunit gene expression in supragranular glutamatergic neurons across New World Monkeys, Old-World Monkeys, and great apes in single nucleus RNA-sequencing datasets. Using Patch-seq recordings from acute and cultured brain slices, we found robust HCN-dependent physiological properties in supragranular pyramidal neurons in a species of New-World monkey (Saimiri sciureus) and two species of Old-World Monkey (Macaca mulatta, Macaca nemestrina). In both human and macaque neocortex, HCN-related intrinsic properties increased in magnitude with increasing laminar depth, especially in one transcriptomic cell type. Within this type, HCN dependent properties were more pronounced in macaque than human neurons. These findings indicate that HCN-governed membrane properties and sensitivity to delta/theta band frequencies are roughly conserved in supragranular pyramidal neurons across at least 36 million years of primate evolution.

Source connections

Published article ↗

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Radaelli, C., Schmitz, M., Liu, X.-P., Sawchuk, S., Opitz-Araya, X., Hudson, M., Taskin, N., Bertagnolli, D., Goldy, J., Ko, A. L., Grannan, B. L., Hauptman, J. S., Patel, A. P., Cobbs, C., Smith, K. A., Spain, W. J., Lein, E. S., Bakken, T., Dembrow, N. C., Ting, J. T., Kalmbach, B. E.. 2025-08-24. HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species. https://doi.org/10.1101/2025.08.22.671856

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Attention Across Scales: From Individual Variation to Social Hierarchies and Brain Networks in Semi-Free-Ranging Macaques

Attention is a fundamental brain function supporting perception, decision-making, and social behavior, and its dysfunction profoundly impairs daily life. It is both dynamic and stable, varying across observations and individuals, changing across the lifespan, and being shaped by social and environmental experience. Yet capturing this complexity remains a central challenge in neuroscience. Here, we integrated longitudinal behavioral assessments of semi-free-ranging macaques living in naturalistic social groups with resting-state fMRI. We quantified performance across days, ages, and social hierarchies and related it to intrinsic brain organization. Distinct attentional phenotypes emerged, including individuals with reduced attentional control. Performance followed an inverted-U lifespan trajectory, improving from childhood to adulthood before declining. Social status modulated attentional performance. Critically, nonlinear lifespan trajectories and associations with individual attentional differences were most clearly expressed in frontoparietal connectivity. Together, these findings reveal how sustained attention is organized across scales, providing a biological framework for its individual diversity, social modulation, and neural basis.

neuroscience↗

bioRxiv2026

Decoding natural scenes from patterned optogenetic responses in mouse visual cortex

A central challenge in developing visual cortical prostheses is to determine how visual stimuli should be transformed into effective patterns of cortical stimulation. Although advances in stimulation technologies, including optogenetics, provide increasingly precise control over cortical activity, it remains unclear whether artificially evoked activity can reproduce the information content of naturally evoked visual representations. Here we establish a quantitative framework for evaluating visual encoding strategies by decoding cortical responses evoked by natural vision and patterned optogenetic stimulation. We developed a novel dual-modal paradigm in awake mice to bridge the gap between endogenous photostimulation and artificial network driving. By co-expressing the high-performance calcium indicator GCaMP6s and the red-shifted, ultra-sensitive opsin rsChRmine-oScarlet in the primary visual cortex (V1), we successfully translated dynamic natural movie frames into patterned, spatiotemporal optogenetic stimulation. Quantitative comparisons of macro-scale dynamics demonstrated that this patterned optogenetic injection evokes cortical states highly comparable and representationally aligned with those driven by actual visual photostimulation. To systematically evaluate the fidelity of these responses, we developed STAR, a deep learning model featuring spatial and temporal attention mechanisms, and successfully reconstructed the frames of natural movies from V1 signals under both experimental modalities. Collectively, our results demonstrate that complex sensory information can be both naturally encoded and synthetically injected into V1 circuits with high decoding fidelity. This work provides an empirical and computational proof-of-concept for intelligent, closed-loop biomimetic encoders, establishing a robust framework for next-generation cortical visual neuroprostheses and bidirectional brain-machine interfaces.

neuroscience↗

bioRxiv2026

Why Is Spontaneous Blink Timing Informative? An Adaptive Scheduling Perspective

Spontaneous eye blinks have long been linked to cognitive processing, yet how task demands shape blink timing and its relationship to behavioral performance remains unclear. We examined spontaneous blink behavior in 576 adults performing two variants of the Continuous Performance Task (CPT). Blink occurrence and timing were most strongly modulated by the experimental condition in the more demanding CPT-AX task, whereas their association with response time was stronger in the CPT-X task, where more consistent blink timing predicted faster responses. This dissociation suggests that task structure changes not only blink behavior but also the behavioral relevance of blink timing. These findings are consistent with an adaptive scheduling account of spontaneous blinking and provide a conceptual framework for understanding when and why blink timing contains chronometric information about ongoing cognition.

neuroscience↗