Glutamatergic modulation of synaptic plasticity at a PNS vertebrate cholinergic synapse.
The presence and the functionality of a glutamatergic regulation was studied at the frog neuromuscular junction (NMJ), a singly innervated cholinergic synapse. Bath application of glutamate reduced transmitter release without affecting nerve-evoked presynaptic Ca2+ entry and handling. (1S,3R)-aminocyclopentanedicarboxylic acid (ACPD), a metabotropic glutamate receptor (mGluR) agonist, mimicked the effects of glutamate while (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), a mGluR antagonist, blocked glutamate effects. MCPG had no effect on transmitter release evoked at low frequency (0.2 Hz) but significantly reduced synaptic depression (10 Hz, 80 s). This suggests that a frequency-dependent endogenous glutamatergic modulation is present at the frog NMJ and is mediated through mGluRs. Immunohistochemical labelling revealed the presence of mGluRs at the end plate area, primarily on muscle fibers. Functional glutamate uptake machinery was also found at the NMJ as blockade of glutamate transport by the inhibitor dl-threo-beta-benzyloxyaspartate (DL-TBOA) increased high frequency-induced depression, suggesting that the transporters system is used to eliminate glutamate from the extracellular space. Moreover, immunohistochemical labelling revealed that glutamate-aspartate transporters (GLASTs) are predominantly present on perisynaptic Schwann cells (PSCs). However, local application of glutamate on PSCs unreliability evoked small Ca2+ responses. Hence, these data suggest that functional glutamatergic interactions at a purely cholinergic synapse, shape synaptic efficacy and short-term plasticity in a frequency-dependent fashion.
Pinard
Audrée
A
Centre de Recherche en Sciences Neurologiques and Département de physiologie, Université de Montréal, Montréal, Canada,H3C 3J7.
Lévesque
Sébastien
S
Vallée
Joanne
J
Robitaille
Richard
R
D000109:Acetylcholine / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D008954:Models, Biological; D009469:Neuromuscular Junction / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D011894:Rana pipiens; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D027322:Amino Acid Transport System X-AG; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D000109:Acetylcholine; D002118:Calcium