Glutamate at the Vertebrate Neuromuscular Junction: From Modulation to Neurotransmission

Abstract

Although acetylcholine is the major neurotransmitter operating at the skeletal neuromuscular junction of many invertebrates and of vertebrates, glutamate participates in modulating cholinergic transmission and plastic changes in the last. Presynaptic terminals of neuromuscular junctions contain and release glutamate that contribute to the regulation of synaptic neurotransmission through its interaction with pre- and post-synaptic receptors activating downstream signaling pathways that tune synaptic efficacy and plasticity. During vertebrate development, the chemical nature of the neurotransmitter at the vertebrate neuromuscular junction can be experimentally shifted from acetylcholine to other mediators (including glutamate) through the modulation of calcium dynamics in motoneurons and, when the neurotransmitter changes, the muscle fiber expresses and assembles new receptors to match the nature of the new mediator. Finally, in adult rodents, by diverting descending spinal glutamatergic axons to a denervated muscle, a functional reinnervation can be achieved with the formation of new neuromuscular junctions that use glutamate as neurotransmitter and express ionotropic glutamate receptors and other markers of central glutamatergic synapses. Here, we summarize the past and recent experimental evidences in support of a role of glutamate as a mediator at the synapse between the motor nerve ending and the skeletal muscle fiber, focusing on the molecules and signaling pathways that are present and activated by glutamate at the vertebrate neuromuscular junction.

The Neurotransmitters Involved in Drosophila Alcohol-Induced Behaviors

“…In mammals, glutamate functions as the primary excitatory neurotransmitter in the CNS, while in Drosophila, ACh has this role. Conversely, flies use glutamate at the neuromuscular junction, while in mammals, that neurotransmitter is ACh (Colombo and Francolini, 2019). Although flies do have glutamatergic neurons in the CNS, their role has historically not been well-understood (Liu and Wilson, 2013); but recent advancements will be discussed below.…”

Bivalves are NO different: nitric oxide as negative regulator of metamorphosis in the Pacific oyster, Crassostrea gigas

“…Our study showed that in C. gigas larvae CgNOS as well as CgNR1 are both expressed in the foot, particularly near the foot base, supporting this theory of NMDA receptor regulating NO production via intracellular Ca 2+ concentrations and subsequent activation of CgNOS. Co-localisation of NMDA receptors and NOS in vertebrates mostly occur on the postsynaptic side or neuromuscular junctions [ 69 ]. Thus, CgNOS could receive signals from NMDA receptors for further downstream pathways potentially involved in regulating foot glands for cementation [ 47 – 49 ] or muscle fibres ([ 69 ], and references herein), both also located at the base of the foot [ 47 , 70 ].…”

“…Co-localisation of NMDA receptors and NOS in vertebrates mostly occur on the postsynaptic side or neuromuscular junctions [ 69 ]. Thus, CgNOS could receive signals from NMDA receptors for further downstream pathways potentially involved in regulating foot glands for cementation [ 47 – 49 ] or muscle fibres ([ 69 ], and references herein), both also located at the base of the foot [ 47 , 70 ]. Physical interaction between vertebrate transmembrane NMDA receptors and NOS, when not soluble in the cytosol, also exists via postsynaptic density proteins 95 (PSD-95), which binds to the PDZ domains of the NMDA receptor and NOS [ 71 ].…”

Bivalves are NO Different: Nitric Oxide as Negative Regulator of Metamorphosis in the Pacific Oyster, Crassostrea Gigas.

“…Our study showed that in C. gigas larvae CgNOS as well as CgNR1, the NMDA receptor subunit 1, are both expressed in the foot, particularly near the foot base, supporting this theory of NMDA receptor regulating NO production via intracellular Ca 2+ concentrations and subsequent activation of CgNOS. Colocalisation of NMDA receptors and NOS in vertebrates mostly occur on the postsynaptic side or neuromuscular junctions (68). Thus, CgNOS could receive signals from NMDA receptors for further downstream pathways potentially involved in regulating foot glands for cementation (46)(47)(48) or muscle bres ( 68, and references herein), both also located at the base of the foot (46,69).…”