The astrocyte α1A‐adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex

Author:

Wahis Jérôme123ORCID,Akkaya Cansu12ORCID,Kirunda Andre M.12ORCID,Mak Aline12ORCID,Zeise Karen12ORCID,Verhaert Jens12,Gasparyan Hayk45ORCID,Hovhannisyan Sargis45ORCID,Holt Matthew G.1236ORCID

Affiliation:

1. Laboratory of Glia Biology VIB‐KU Leuven Center for Brain and Disease Research Leuven Belgium

2. Department of Neurosciences KU Leuven Leuven Belgium

3. Leuven Brain Institute Leuven Belgium

4. Department of Mathematics and Mechanics Yerevan State University Yerevan Armenia

5. Armenian Bioinformatics institute Yerevan Armenia

6. Instituto de Investigação e Inovação em Saúde (i3S) University of Porto Porto Portugal

Abstract

AbstractNoradrenaline (norepinephrine) is known to modulate many physiological functions and behaviors. In this study, we tested to what extent astrocytes, a type of glial cell, participate in noradrenergic signaling in mouse primary visual cortex (V1). Astrocytes are essential partners of neurons in the central nervous system. They are central to brain homeostasis, but also dynamically regulate neuronal activity, notably by relaying and regulating neuromodulator signaling. Indeed, astrocytes express receptors for multiple neuromodulators, including noradrenaline, but the extent to which astrocytes are involved in noradrenergic signaling remains unclear. To test whether astrocytes are involved in noradrenergic neuromodulation in mice, we employed both short hairpin RNA mediated knockdown as well as pharmacological manipulation of the major noradrenaline receptor in astrocytes, the α1A‐adrenoreceptor. Using acute brain slices, we found that the astrocytic α1A‐adrenoreceptor subtype contributes to the generation of large intracellular Ca2+ signals in visual cortex astrocytes, which are generally thought to underlie astrocyte function. To test if reduced α1A‐adrenoreceptor signaling in astrocytes affected the function of neuronal circuits in V1, we used both patch‐clamp and field potential recordings. These revealed that noradrenergic signaling through the astrocyte α1A‐adrenoreceptor is important to not only modulate synaptic activity but also to regulate plasticity in V1, through the potentiation of synaptic responses in circuits involved in visual information processing.

Funder

Fonds Wetenschappelijk Onderzoek

Horizon 2020 Framework Programme

Onderzoeksraad, KU Leuven

European Research Council

Publisher

Wiley

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