Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal mice

Abstract

A controlled, periodic exchange of air between lungs and atmosphere requires a neuronal rhythm generated by a network of neurons in the ventral respiratory group (VRG) of the brainstem. Glial cells, e.g. astrocytes, have been shown to be supportive in stabilizing this neuronal activity in the central nervous system during development. In addition, a variety of neuromodulators including serotonin (5-HT), Substance P (SP), and thyrotropin-releasing hormone (TRH) stimulate respiratory neurons directly. If astrocytes in the VRG, like their neuronal neighbors, are also directly stimulated by neuromodulators, they might indirectly affect the respiratory neurons and consequently the respiratory rhythm. In the present study, we provide support for this concept by demonstrating expression of NK1-R, TRH-R, and 5-HT(2)-R in astrocytes of the VRG with immunohistochemistry. Additionally, we showed that the external application of the neuromodulators 5-HT, SP, and TRH activate calcium transients in VRG astrocytes. Consequently, we postulate that in the VRG of the neonatal mouse, neuromodulation by SP, TRH, and serotonin also involves astrocytic calcium signaling.

Glia Contribute to the Purinergic Modulation of Inspiratory Rhythm-Generating Networks

“…In addition, glia cultured from the preBötC have minimal SP sensitivity (Fig. 6), which is consistent with recent observations in slices that only a portion of glia in the preBötC region respond to SP with small increases in intracellular Ca 2ϩ (Härtel et al, 2009). Furthermore, while cultured glia express NK1R mRNA (Too et al, 1994), glia in guinea pig (Yip and Chahl, 2001) and human brain (Tooney et al, 2000) do not express NK1R protein.…”

Determinants of Functional Coupling between Astrocytes and Respiratory Neurons in the Pre-Bötzinger Complex

“…Astrocytes in the preBötC network are responsive to glutamate [22] and Ca 2+ transients can be evoked by application of glutamate [15], [23]. In this paper we were able to show that metabotropic glutamate receptors coupled to the PLC/IP3 pathway play a role for glutamate induced astroglial calcium signaling in the preBötC.…”

“…Previous studies from this laboratory demonstrated that glutamate triggers calcium signaling in astrocytes of the ventral respiratory region of the medulla [15], [23], and other studies have shown that group I metabotropic glutamate receptors promote calcium release from intracellular stores and couple neuronal activity to calcium signals in nearby astrocytes of rat cortex, hippocampus and suprachiasmatic nucleus [24], [25].…”

“…Transmitter molecules and modulators released from neurons have been shown to elicit astroglial calcium signals in many parts of the central nervous system [28], [29] including the respiratory network [15], [16]. Through intercellular coupling via gap junctions or by the astroglial release of glutamate, and also ATP or D-serine, the calcium signal can spread to other astrocytes or affect neuronal excitability.…”

“…Astrocytes express K + channels (Kir4.1; KCNJ10) that maintain potassium homeostasis and the resting membrane potential of astrocytes in the medulla [14]. Several authors recently reported that astrocytes in the respiratory network respond to prevailing neuromodulators with an increase of intracellular calcium concentration [15], [16], [17]. Two consequences of elevated [Ca 2+ ] in astrocytes have been suggested: astroglial neurotransmitter release that influences activity of nearby neurons [18], [19], [20], [21], and effects on central CO 2 /pH-chemosensitivity [17].…”