Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?

Abstract

Fast chemical synaptic transmission is a major form of neuronal communication in the nervous system of mammals. Another important, but very different, form of intercellular communication is volume transmission, which is a slower non‐synaptic signaling. The amino acid glutamate is the most abundant excitatory neurotransmitter in the nervous system, which mediates both synaptic and non‐synaptic signaling via ionotropic and metabotropic glutamate receptors. Intriguingly, neurons establish glutamatergic synapses also with oligodendrocyte precursor cells (NG2+‐glia). Moreover, neuronal activity and glutamate receptors play an important role in the development and functionality of oligodendrocytes and their precursors in vivo. Yet, molecular characteristics and functional significance of neuron–glia synapses remain poorly understood, and it is unclear how glutamate receptors mediate the effects of neuronal activity on the oligodendrocyte lineage cells. In this review, we discuss what is known with regard to synaptic and non‐synaptic glutamatergic signaling between neurons and oligodendrocyte lineage cells, what can be suggested based on the current state of knowledge, and what is fully unknown and requires new research.

Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development—A study in the zebrafish model

“…Other studies putting forward this hypothesis indicate that some forms of neuronal activity facilitate proliferation (Chen et al, 2018;Mount & Monje, 2017), while others boost differentiation (Chen et al, 2018;Nagy et al, 2017). In this context, similar to our study where we manipulate glutamate signaling using iGluSnFR as a genetic tool, in 2017 Kougioumtzidou et al, showed that genetic disruption of glutamatergic receptors in OPCs promoted apoptotic death of oligodendrocytes, which indicated that axon-OPC synapses are considered as critical for the structural and functional communication between the two cell types (Kukley et al, 2007;Kula et al, 2019), even though we could not see any obvious apoptotic effect in our study in the fish now.…”

Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

“…Furthermore, the Fisher’s exact test was carried out to calculate the similarity between the different networks based on the training data and the test data, respectively, and the result showed a p -value very close to 0 (1e-23238, 1e-131120, 1e-3103, 1e-44540, and 1e-139070 for AD, PD, PSP, FTD, and all NDs, respectively). In addition, the node with the highest degree in the network was also significantly correlated with maintaining cellular homeostasis ( Table 4 ; Crowe et al, 1994 ; Dong et al, 1997 ; Keats et al, 2007 ; Tang et al, 2011 ; Kaneko et al, 2016 ; Kula et al, 2019 ; Anerillas et al, 2020 ).…”

Microenvironmental interactions of oligodendroglial cells

“…Glutamate is the most abundant excitatory neurotransmitter in the CNS and mediates both synaptic and non-synaptic signaling (Kula et al, 2019). OPCs express a variety of ionotropic and metabotropic glutamate receptors (Barres et al, 1990;Borges et al, 1994).…”