The astrocyte α1-adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex

ABSTRACT Noradrenaline (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 knocked down the major noradrenaline receptor in astrocytes, the α1A- adrenoreceptor. Using this model, we found that the α1A-adrenoreceptor is involved in triggering intracellular calcium transients in astrocytes, which are generally thought to underlie astrocyte function. To test if impaired α1A-adrenoreceptor signaling in astrocytes affected the function of neuronal circuits in V1, we used electrophysiological measurements and found that noradrenergic signaling through astrocyte α1A-adrenoreceptor controls the basal level of inhibition and regulates plasticity in V1 by potentiating synaptic responses in circuits involved in visual information processing. MAIN POINTS The α1A-adrenoreceptor (α1A-NAR) is the major α1-NAR in primary visual cortex (V1) α1A-NAR signaling triggers astrocyte Ca 2+ responses in V1. Astrocyte α1A-NARs play a key role in regulating basal inhibitory transmission and are crucial for LTP induction in V1