Emerging role of astrocytes in oxytocin-mediated control of neural circuits and brain functions.

The neuropeptide oxytocin has been in the focus of scientists for decades due to its profound and pleiotropic effects on physiology, activity of neuronal circuits and behaviors, among which sociality. Until recently, it was believed that oxytocinergic action exclusively occurs through direct activation of neuronal oxytocin receptors. However, several studies demonstrated the existence and functional relevance of astroglial oxytocin receptors in various brain regions in the mouse and rat brain. Astrocytic signaling and activity is critical for many important physiological processes including metabolism, neurotransmitter clearance from the synaptic cleft and integrated brain functions. While it can be speculated that oxytocinergic action on astrocytes predominantly facilitates neuromodulation via the release of specific gliotransmitters, the precise role of astrocytic oxytocin receptors remains elusive. In this review, we discuss the latest studies on the interaction between the oxytocinergic system and astrocytes, including detailed information about intracellular cascades, and speculate about future research directions on astrocytic oxytocin signaling.

Calcium imaging and BAPTA loading of amygdala astrocytes in mouse brain slices.

Astrocytes are glial cells that exhibit calcium signaling-mediated activity. Here, we present a protocol to monitor and manipulate astrocyte calcium activity from mouse amygdala slices. In the first part of this protocol, we describe the procedure of astrocyte calcium imaging. In the second part, we detail how to disrupt astrocyte calcium activity by patch-clamp-mediated loading of BAPTA. These two approaches are presented separately but they can also be used simultaneously to monitor the effects of disruption on an astrocyte network. For complete details on the use and execution of this protocol, please refer to Wahis et al. (2021).

[Emergent role of astrocytes in oxytocin-mediated modulatory control of neuronal circuits and brain functions]. / Rôle émergent des astrocytes dans le contrôle des circuits neuronaux et des fonctions cérébrales modulés par l'ocytocine.

The neuropeptide oxytocin has been in the focus of scientists for decades due to its profound and pleiotropic effects on physiology, activity of neuronal circuits and behaviors. Until recently, it was believed that oxytocinergic action exclusively occurs through direct activation of neuronal oxytocin receptors. However, several studies demonstrated the existence and functional relevance of astroglial oxytocin receptors in various brain regions in the mouse and rat brain. Astrocytic signaling and activity are critical for many important physiological processes including metabolism, neurotransmitter clearance from the synaptic cleft and integrated brain functions. While it can be speculated that oxytocinergic action on astrocytes predominantly facilitates neuromodulation via the release of gliotransmitters, the precise role of astrocytic oxytocin receptors remains elusive. In this review, we discuss the latest studies on the interaction between the oxytocinergic system and astrocytes, and give details of underlying intracellular cascades.

Title: Rôle émergent des astrocytes dans le contrôle des circuits neuronaux et des fonctions cérébrales modulés par l'ocytocine. Abstract: L'ocytocine est un neuropeptide au centre de l'attention des scientifiques depuis des décennies, en raison de ses effets puissants et pléiotropes tant sur le plan physiologique que sur l'activité des circuits neuronaux, modulant ainsi nos comportements. Jusqu'à une date récente, on pensait que l'action de l'ocytocine était induite exclusivement par l'activation directe de ses récepteurs neuronaux. Cependant, plusieurs études ont démontré l'existence et la pertinence fonctionnelle des récepteurs astrogliaux de l'ocytocine dans diverses régions du cerveau de la souris et du rat. La signalisation et l'activité astrocytaires sont essentielles à de nombreux processus physiologiques importants, notamment le métabolisme, l'élimination des neurotransmetteurs de la fente synaptique et les fonctions cérébrales intégrées. Bien que l'on puisse supposer que l'action de l'ocytocine sur les astrocytes facilite principalement la neuromodulation via la libération de gliotransmetteurs, le rôle précis des récepteurs astrocytaires de l'ocytocine reste difficile à cerner. Dans cette revue, nous discutons des dernières études sur l'interaction entre le système ocytocinergique et les astrocytes, et décrivons les cascades intracellulaires mises en jeu.

Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents.

Oxytocin (OT) orchestrates social and emotional behaviors through modulation of neural circuits. In the central amygdala, the release of OT modulates inhibitory circuits and, thereby, suppresses fear responses and decreases anxiety levels. Using astrocyte-specific gain and loss of function and pharmacological approaches, we demonstrate that a morphologically distinct subpopulation of astrocytes expresses OT receptors and mediates anxiolytic and positive reinforcement effects of OT in the central amygdala of mice and rats. The involvement of astrocytes in OT signaling challenges the long-held dogma that OT acts exclusively on neurons and highlights astrocytes as essential components for modulation of emotional states under normal and chronic pain conditions.

Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons.

Oxytocin (OT) is a great facilitator of social life but, although its effects on socially relevant brain regions have been extensively studied, OT neuron activity during actual social interactions remains unexplored. Most OT neurons are magnocellular neurons, which simultaneously project to the pituitary and forebrain regions involved in social behaviors. In the present study, we show that a much smaller population of OT neurons, parvocellular neurons that do not project to the pituitary but synapse onto magnocellular neurons, is preferentially activated by somatosensory stimuli. This activation is transmitted to the larger population of magnocellular neurons, which consequently show coordinated increases in their activity during social interactions between virgin female rats. Selectively activating these parvocellular neurons promotes social motivation, whereas inhibiting them reduces social interactions. Thus, parvocellular OT neurons receive particular inputs to control social behavior by coordinating the responses of the much larger population of magnocellular OT neurons.