Role of astrocytes in rhythmic motor activity

Abstract

Rhythmic motor activities such as breathing, locomotion, tremor, or mastication are organized by groups of interconnected neurons. Most synapses in the central nervous system are in close apposition with processes belonging to astrocytes. Neurotransmitters released from neurons bind to receptors expressed by astrocytes, activating a signaling pathway that leads to an increase in calcium concentration and the release of gliotransmitters that eventually modulate synaptic transmission. It is therefore likely that the activation of astrocytes impacts motor control. Here we review recent studies demonstrating that astrocytes inhibit, modulate, or trigger motor rhythmic behaviors.

FIGURE 1

Schematic representation of the tripartite synapse. Left: astrocytes (green) are in close contact with blood vessels and synapses. Inset: in addition to postsynaptic receptors, neurotransmitters activate receptors expressed by astrocyte. This induces an increase in intracellular Ca²⁺ concentration, which triggers the release of gliotransmitters that interact with pre‐ and postsynaptic receptors

FIGURE 2

Astrocytes contribute to the modulation of breathing in response to changes in pH and pCO₂. (a) Anatomical organization of the brainstem circuits responsible for breathing. pF_v: ventral parafacial nucleus, also known as RTN: retrotrapezoid nucleus. preBötC: preBötzinger complex. pF: parafacial nucleus. pF_l: lateral parafacial nucleus. pF_v: ventral parafacial nucleus. LRN: lateral reticular nucleus. NA: nucleus ambiguus. preBötC: preBötzinger complex. BötC: Bötzinger complex. rVRG: rostral ventral respiratory group. cVRG: caudal ventral respiratory group. (b) Ca²⁺ response of astrocytes in the pF_v (RTN) to acidification. (c) Response of neurons from the pF_v (RTN) and of phrenic nerve to the optogenetic activation of pF_v (RTN) astrocytes. b and c are adapted from (Gourine et al., 2010), with permission. (d) Hypothetical mechanisms for the regulation of breathing by pF_v (RTN) astrocytes. Astrocytes sense CO₂ increase via CO₂‐sensitive connexin (Cx) hemichannels which directly release ATP. Acidification activates the Na⁺/HCO₃ ⁻ co‐transport (NBC), which in turn activates the Na⁺/Ca²⁺ exchange (NCX). The increase in intracellular Ca²⁺ leads to the Ca²⁺‐dependent vesicular release of ATP. ATP is likely to act on several downstream targets, including neighboring astrocytes, smooth muscle cells, and neurons

FIGURE 3

Astrocytes mediate futility‐induced passivity in larval zebrafish. (a) In closed loop, the visual feedback is adjusted to the motor activity. In open loop, the visual feedback does not match motor activity. After repeated motor failures, the animals enter a passive motor state. (b) Neuronal and glial Ca²⁺ aligned to passivity onset. (c) Whole‐brain neuronal and glial Ca²⁺ before, during, and after passivity onset. (d) The ablation of astrocytes in the lateral medulla oblongata reduces futility‐induced passivity. Adapted from (Mu et al., 2019), with permission

FIGURE 4

Astrocytes trigger burst firing in the masticatory CPG. (a) Anatomical organization of mastication. The main jaw opener (digastric muscle) and closer (masseter) are innervated by motoneurons from NVmot which receive inputs from NVsnpr. (b) Schematic representation of the cellular mechanism. Glutamate released from sensory trigeminal neurons activates astrocytic NMDA receptors in NVsnpr. This induces the secretion of S100ß via a Ca²⁺‐dependent mechanism. The resulting decrease in extracellular free Ca²⁺ promotes I_NaP and burst firing in neighbor neurons. NVsnpr: trigeminal main sensory nucleus. NVmot: trigeminal main motor nucleus. For details, see Morquette et al. (2015)