ACTIVATION OF PHARMACOLOGICALLY DISTINCT METABOTROPIC GLUTAMATE RECEPTORS DEPRESSES RETICULOSPINAL-EVOKED MONOSYNAPTIC EPSPS IN THE LAMPREYSPINAL-CORD

1. Different metabotropic glutamate receptors (mGluRs) can modulate sy naptic transmission in different regions in the CNS, but their roles a t individual synaptic connections have not been detailed. We used pair ed intracellular recordings from reticulospinal axons and their postsy naptic target neurons in the lamprey spinal cord to investigate the ef fects of mGluR activation on glutamatergic synaptic transmission. 2. T he mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [ (1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both re duced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The d epression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, t he mGluR agonists did not affect the amplitude of lpha-amino-3-hydroxy -5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Ta ken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 d epress reticulospinal synaptic transmission via presynaptic mechanisms . 3. (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), which selec tively activates group II mGluRs, also reduced the amplitude of reticu lospinal-evoked EPSPs without any apparent change in the input resista nce or membrane potential of the postsynaptic neuron. 4. The mGluR ant agonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coappli cation of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they i nhibit synaptic transmission by an action on pharmacologically distinc t mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reti culospinal axon in the lamprey. These presynaptic mGluRs could serve a s glutamatergic autoreceptors limiting the extent of reticulospinal-me diated excitation of spinal neurons.