Biology subjects

Hirnet, D.

Publications and source records attributed to Hirnet, D..

3 recordsLinked to original sources

bioRxiv2026

Cell-type specific astrocyte activation is driven by cortical top-down modulation

Cortical projections to cortical and subcortical targets provide top-down modulation that shapes neuronal performance, including gain control and excitation-inhibition balance. However, the contribution of astrocytes to this process remains poorly understood. In the olfactory bulb, the first relay station of odor information processing, bottom-up input is transmitted from olfactory sensory neurons to mitral/tufted (M/T) cells, which project to the olfactory cortex. Context- and state-dependent top-down modulation arises from feedback projections originating in the anterior piriform cortex (aPC) that target granule cells (GCs). We examined how astrocytes respond to bottom-up and top-down neuronal activity using confocal Ca{superscript 2} imaging, cell-type-specific optogenetics, electrical stimulation, and single-cell electrophysiology. We found that Ca{superscript 2} signals in astrocytes are selectively triggered by action potential-dependent ATP release from GCs while M/T cells failed to elicit significant astrocytic responses. Although synaptic input from M/T cells depolarized GCs, it was insufficient to induce action potential firing and subsequent astrocyte activation. By contrast, glutamatergic top-down input from the aPC evoked sustained GC firing, leading to ATP-dependent Ca{superscript 2} signaling in astrocytes. Our results reveal an unappreciated level of complexity in neuron-astrocyte communication, highlighting its cell-type specificity as well as its context- and state-dependence.

neuroscience↗

bioRxiv2025

Crosstalk of noradrenergic Ca2+ and cAMP signaling in astrocytes of the murine olfactory bulb

Cyclic adenosine monophosphate (cAMP) and Ca2+ are ubiquitous second messengers that regulate gene expression, metabolism, and synaptic plasticity. Here, we identified a complex interplay between Ca2+ and cAMP signaling pathways in mouse olfactory bulb astrocytes. Norepinephrine (NE) elevated both Ca2+ and cAMP levels via 1 and 2 adrenergic receptors, whereas {beta} receptors triggered only cAMP responses. The 1 receptor agonist phenylephrine increased cAMP, but this effect was suppressed when Ca2+ elevations were blocked by Ca2+ depletion and removal of external Ca2+. We found that 1A and 1D receptors are key targets for phenylephrine, acting through Ca2+/calmodulin-dependent adenylyl cyclases AC1 and AC3 downstream of 1 receptor activation. Moreover, 2 receptor stimulation raised Ca2+ levels, thereby stimulating cAMP production, yet also reduced forskolin-induced cAMP elevations, indicating that 2 receptors can both inhibit adenylyl cyclase via Gi and stimulate AC1/AC3 via Ca2+ signaling. Together, these findings reveal intricate crosstalk between noradrenergic Ca2+ and cAMP signaling in olfactory bulb astrocytes mediated by all three adrenergic receptor subtypes.

neuroscience↗

bioRxiv2024

Microgliosis, astrogliosis and loss of aquaporin-4 polarity in frontal cortex of COVID-19 patients

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), causing human coronavirus disease 2019 (COVID-19), not only affects the respiratory tract, but also impacts other organs including the brain. A considerable number of COVID-19 patients develop neuropsychiatric symptoms that may linger for weeks and months and contribute to "long-COVID". While the neurological symptoms of COVID-19 are well described, the cellular mechanisms of neurologic disorders attributed to the infection are still enigmatic. Here, we studied the effect of an infection with SARS-CoV-2 on the structure and expression of marker proteins of astrocytes and microglial cells in the frontal cortex of patients who died from COVID-19 in comparison to non-COVID-19 controls. Most of COVID-19 patients had microglial cells with retracted processes and rounded and enlarged cell bodies in both gray and white matter, as visualized by anti-Iba1 staining and confocal fluorescence microscopy. In addition, gray matter astrocytes in COVID-19 patients were frequently labeled by intense anti-GFAP staining, whereas in non-COVID-19 controls, most gray matter astrocytes expressed little GFAP. The most striking difference between astrocytes in COVID-19 patients and controls was found by anti-aquaporin-4 (AQP4) staining. In COVID-19 patients, a large number of gray matter astrocytes showed an increase in AQP4. In addition, AQP4 polarity was lost and AQP4 covered the entire cell, including the cell body and all cell processes, while in controls, AQP4 immunostaining was mainly detected in endfeet around blood vessels and did not visualize the cell body. In summary, our data suggest neuroinflammation upon SARS-CoV-2 infection including microgliosis and astrogliosis, including loss of AQP4 polarity.

neuroscience↗