Satellite glial cells modulate cholinergic transmission between sympathetic neurons

Abstract

Satellite glial regulation of sympathetic activity" 15 16 17 18 40 Introduction 41 Glial cells, once thought of as neuron support cells, are now recognized as 42 active players in the formation and function of normal brain circuitry [1, 2]. 43 Astrocytes, the most abundant glial cell type in the brain, regulate many properties 44 of neuronal circuits such as neuronal excitability, synaptic transmission and 45 plasticity [3-5]. Their role at central nervous system (CNS) synapses has been the 46 focus of a number of studies in the past two decades, showing that astrocytes control 47 4 61 under pathological conditions such as hypertension and chronic heart disease [20, 62 21]. Sympathetic tone is initially set by neurons present in the brain and spinal cord 63 [22], with the sympathetic ganglionic neurons acting as the final regulatory element 64 determining the output of the sympathetic circuit. 65 A striking anatomical feature of the sympathetic ganglion is the presence of 66 satellite glia that form an envelope around individual ganglionic neuronal somata 67 and cover synapses [23]. This is in contrast to the CNS where individual astrocytes 68 are in contact with multiple neurons [24]. While the function of the satellite glia 69 remains to be fully defined, both sympathetic and sensory satellite glia share several 70 cellular and molecular features with astrocytes, including expression of 71 neurotransmitter receptors and the formation of a glia network via gap junctions 72 [25]. Satellite glia injury responses are characterized by changes in expression 73 profiles, including an up-regulation of the activation marker glial fibrillary acidic 74 protein (GFAP) [26]. These findings point to a possible effect in disease progression 75 and suggest that satellite glia play roles in both normal function and disease in the 76 peripheral nervous system. 77 Recent studies using genetic manipulations of sympathetic satellite glia have 78 implicated these cells in the regulation of target organ function by demonstrating 79 that selective activation of Gq-GPCR (G protein-coupled receptor) signaling in 80 peripheral glia leads to the modulation of cardiac properties in adult mice [27, 28]. 81 These effects are mediated through postganglionic sympathetic innervation of the 82 heart raising the possibility that activated glia influence the active properties of 157 in 4% paraformaldehyde (PFA) and then cryo-protected by incubating them in 30%

Satellite glia are essential modulators of sympathetic neuron survival, activity, and autonomic function

“…Satellite glia could influence neuronal activity via regulation of ganglionic levels of acetylcholine, the major neurotransmitter released by pre-ganglionic axons. Despite previous observations that satellite glia modulate cholinergic neurotransmission in co-cultured sympathetic neurons (Enes et al, 2020;Feldman-Goriachnik et al, 2018), we did not detect glial transcripts involved in cholinergic signaling using single-cell RNA sequencing of sympathetic ganglia (Mapps et al, 2021). However, we do not exclude glia-mediated effects on synapse formation during development or maintenance (Enes et al, 2020).…”

“…Despite previous observations that satellite glia modulate cholinergic neurotransmission in co-cultured sympathetic neurons (Enes et al, 2020;Feldman-Goriachnik et al, 2018), we did not detect glial transcripts involved in cholinergic signaling using single-cell RNA sequencing of sympathetic ganglia (Mapps et al, 2021). However, we do not exclude glia-mediated effects on synapse formation during development or maintenance (Enes et al, 2020). Another potential mechanism could involve glial regulation of extracellular ATP and/or its break-down products in the neuronal micro-environment (Hanani, 2010).…”

“…This unique arrangement places satellite glial cells in an ideal position to be critical regulators of neuronal connectivity, synaptic transmission, and homeostasis. Studies in sympathetic neuron-glia cocultures have suggested roles for satellite glia in promoting dendrite growth, synapse formation, modulating extracellular ion and neurotransmitter concentrations, and regulating synaptic transmission (Enes et al, 2020;Feldman-Goriachnik et al, 2018;Hanani, 2010;Tropea et al, 1988). Satellite glia also envelop neuronal cell bodies in sensory ganglia in the peripheral nervous system (PNS) (Hanani and Spray, 2020).…”