Excitation of cerebellar interneurons by group I metabotropic glutamate receptors.
Cerebellar basket and stellate neurons (BSNs) provide feed-forward inhibition to Purkinje neurons (PNs) and thereby play a principal role in determining the output of the cerebellar cortex. During low-frequency transmission, glutamate released at parallel fiber synapses excites BSNs by binding to AMPA receptors; high-frequency transmission also recruits N-methyl-d-aspartate (NMDA) receptors. We find that, in addition to these ligand-gated receptors, a G-protein-coupled glutamate receptor subtype participates in exciting BSNs. Stimulation of metabotropic glutamate receptor 1alpha (mGluR1alpha) with the mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) leads to an increase in spontaneous firing of BSNs and indirectly to an increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in PNs. Under conditions in which ligand-gated glutamate receptors are blocked, parallel fiber stimulation generates a slow excitatory postsynaptic current (EPSC) in BSNs that is inhibited by mGluR1alpha-selective antagonists. This slow EPSC is capable of increasing BSN spiking and indirectly increasing sIPSCs frequency in PNs. Our findings reinforce the idea that distinct subtypes of glutamate receptors are activated in response to different patterns of activity at excitatory synapses. The results also raise the possibility that mGluR1alpha-dependent forms of synaptic plasticity may occur at excitatory inputs to BSNs.
Karakossian
Movses H
MH
Dept. of Neurobiology, UCLA Medical Center, 650 Charles Young Drive, Box 951763, Los Angeles, CA 90095-1763, USA.
Otis
Thomas S
TS
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology
D001565:Benzoates; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079694:alpha-methyl-4-carboxyphenylglycine; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine