Cortical astrocyte histamine-1-receptors regulate intracellular calcium and extracellular adenosine dynamics across sleep and wake

Astrocytes in mammalian cortex express particularly high levels of the wake-promoting histamine-1-receptor (H1R), yet little is known about how astrocytic H1R contributes to arousal regulation. To address this gap, we test how astrocyte-specific H1R signaling in murine cortex affects local astrocyte calcium (Ca2+), sleep/wake dynamics, and extracellular adenosine—an astrocytic output that regulates cortical arousal. Using ex vivo two-photon Ca2+ imaging in acute cortical slices, we show that H1R mediates cell-autonomous astrocyte Ca2+ responses to histamine and attenuates responses to norepinephrine. Next, using freely moving fiber photometry and electroencephalogram/electromyogram recordings, we show that astrocyte-specific H1R deletion in cortex promotes wakefulness, reduces REM sleep, and alters astrocyte Ca2+ signals during wake and extracellular adenosine dynamics around REM transitions. Our data indicate that H1R activity not only mediates histamine responses in astrocytes but als..., , # **Cortical astrocyte histamine-1-receptors regulate intracellular calcium and extracellular adenosine dynamics across sleep and wake**

Dataset DOI: [10.5061/dryad.2280gb64x](10.5061/dryad.2280gb64x)

**Overview**

This data package contains *ex vivo* slice imaging data and *in vivo* photometry/electrophysiology data supporting the manuscript titled above. *Ex vivo* data support Figs. 1–5 and S1–S3; *in vivo* data support Figs. 6–8 and S4–S7. File and folder names indicate the main figure(s) each dataset supports. Code used to generate all figures is archived in the accompanying Zenodo repository (DOI: 10.5281/zenodo.16809849).

#### ***Ex vivo*** **slice data**

**Data shown in figures 1–2, 4 and S1, S3:**

Fig1_DoseResponse_data.mat

Fig1.zip

Fig2_H1Rpharm_data.mat

Fig2.zip

Fig4_H1RKO_HA_data.mat

Fig4_H1RKO_NE_data.mat

Fig4_H1RKO_NE_postHA_data.mat

Fig4.zip

Datasets are named by figure and experiment. Each dataset includes:

1.   .mat file containing:

a.     Cell array stori...,