title: Mixed inhibitory synaptic balance correlates with glutamatergic synaptic phenotype in cerebellar unipolar brush cells.
abstract: Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory-inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABA(A) receptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.
authors.affiliation: Inhibitory Transmission Team, Institut de Biologie de l'ENS, IBENS, Inserm, U1024, CNRS, UMR 8197, Paris, F-75005 France.
authors.forename: Charly V
authors.initials: CV
authors.lastname: Rousseau
authors.forename: Guillaume P
authors.initials: GP
authors.lastname: Dugué
authors.forename: Andréa
authors.initials: A
authors.lastname: Dumoulin
authors.forename: Enrico
authors.initials: E
authors.lastname: Mugnaini
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dieudonné
authors.forename: Marco A
authors.initials: MA
authors.lastname: Diana
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D005998:Glycine / Q000502:physiology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D018684:Glycine Agents; D018009:Receptors, Glycine; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid; D005998:Glycine