title: Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord.
abstract: 1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Krieger
authors.forename: A
authors.initials: A
authors.lastname: el Manira
authors.forename: S
authors.initials: S
authors.lastname: Grillner
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007798:Lampreys; D009434:Neural Pathways / Q000187:drug effects; D018408:Patch-Clamp Techniques; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D012154:Reticular Formation / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D000613:Aminobutyrates; D001565:Benzoates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine