Target-Dependent Use of Coreleased Inhibitory Transmitters at Central Synapses

Dugué, Guillaume P.

doi:10.1523/jneurosci.1500-05.2005

Cited by 236 publications

(235 citation statements)

References 80 publications

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“…(Vestibulocerebellar) UBCs are also innervated by Golgi cells, which co-release GABA and glycine at these synapses. The UBC response, however, was found to be either mixed GABAergic and glycinergic, or purely glycinergic (Dugue et al 2005). It is currently not known whether diVerences in GABA A -receptor mediated responsiveness of UBCs reXect functional heterogeneity, or are due to diVerential maturation/diVerentiation of UBCs at postnatal days Fig.…”

Section: Unipolar Brush Cellsmentioning

confidence: 97%

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

Schilling

Oberdick

Rossi

et al. 2008

Histochem Cell Biol

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Ever since the groundbreaking work of Ramon y Cajal, the cerebellar cortex has been recognized as one of the most regularly structured and wired parts of the brain formed by a rather limited set of distinct cells. Its rather protracted course of development, which persists well into postnatal life, the availability of multiple natural mutants, and, more recently, the availability of distinct molecular genetic tools to identify and manipulate discrete cell types have suggested the cerebellar cortex as an excellent model to understand the formation and working of the central nervous system. However, the formulation of a unifying model of cerebellar function has so far proven to be a most cantankerous problem, not least because our understanding of the internal cerebellar cortical circuitry is clearly spotty. Recent research has highlighted the fact that cerebellar cortical interneurons are a quite more diverse and heterogeneous class of cells than generally appreciated, and have provided novel insights into the mechanisms that underpin the development and histogenetic integration of these cells. Here, we provide a short overview of cerebellar cortical interneuron diversity, and we summarize some recent results that are hoped to provide a primer on current understanding of cerebellar biology.

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Section: Unipolar Brush Cellsmentioning

confidence: 97%

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

Schilling

Oberdick

Rossi

et al. 2008

Histochem Cell Biol

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“…The peak of this late positive wave was quantified, and the analysis was stopped when the first value above 2 SD was reached. GoC-UBC pairs were considered connected when a short-latency (1.2 Ϯ 0.19 ms, n ϭ 8) IPSC (Dugué et al, 2005) with an amplitude more than four times the SD of baseline noise was apparent in the spike-triggered average.…”

Section: Goc-ubc Paired Recordingsmentioning

confidence: 99%

“…Here, we examine GABA-glycinergic cotransmission at GoCs-UBCs synapses. We have shown previously that vestibulocerebellar UBCs express GABA A Rs and GlyRs to different levels (Dugué et al, 2005). In addition, GoCs contain GABA, glycine, or both neurotransmitters (Ottersen et al, 1988;Simat et al, 2007).…”

Section: Introductionmentioning

confidence: 97%

“…This switch may be caused by either a presynaptic (Nabekura et al, 2004) or a postsynaptic (Keller et al, 2001;González-Forero and Alvarez, 2005) change. Although maturation of both sides occurs (Awatramani et al, 2005;Muller et al, 2006), eventually creating mismatches (Dugué et al, 2005), corelease persists in the adult. Overall, the parameters controlling the exact balance between glycine and GABA inhibition in mixed inhibitory systems remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Rousseau¹,

Dugué²,

Dumoulin³

et al. 2012

J. Neurosci.

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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.

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“…The specificity of transmission in their postsynaptic targets is ensured by the differential expression of receptors. Thus, spontaneous IPSCs in granule cells are mediated selectively by GABA A receptors (39), whereas Golgi cells, Lugaro cells, unipolar brush cells, and possibly other interneurons exhibit either glycinergic or mixed glycinergic/GABAergic currents ( Figure 1) (42,43). At least in Golgi cells, GABA A and glycine receptors can co-exist within a given postsynaptic site (42).…”

Section: Organization Of Gaba a Receptors In The Cerebellar Cortexmentioning

confidence: 99%

Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions

Fritschy

Panzanelli

2006

Cerebellum

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GABA A receptors form heteromeric GABA-gated chloride channels assembled from a large family of subunit genes. In cerebellum, distinct GABA A receptor subtypes, differing in subunit composition, are segregated between cell types and synaptic circuits. The cerebellum therefore represents a useful system to investigate the significance of GABA A receptor heterogeneity. For instance, studies of mice carrying targeted deletion of major GABA A receptor subunit genes revealed the role of a subunit variants for receptor assembly, synaptic targeting, and functional properties. In addition, these studies unraveled mandatory association between certain subunits and demonstrated distinct pharmacology of receptors mediating phasic and tonic inhibition. Although some of these mutants have a profound loss of GABA A receptors, they exhibit only minor impairment of motor function, suggesting activation of compensatory mechanisms to preserve inhibitory networks in the cerebellum. These adaptations include an altered balance between phasic and tonic inhibition, activation of voltageindependent K + conductances, and upregulation of GABA A receptors in interneurons that are not affected directly by the mutation. Deletion of the a1 subunit gene leads to complete loss of GABA A receptors in Purkinje cells. A striking alteration occurs in these mice, whereby presynaptic GABAergic terminals are preserved in the molecular layer but make heterologous synapses with spines, characterized by a glutamatergic-like postsynaptic density. During development of a1 0/0 mice, GABAergic synapses are initially formed but are replaced upon spine maturation. These findings suggest that functional GABA A receptors are required for long-term maintenance of GABAergic synapses in Purkinje cells.

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Target-Dependent Use of Coreleased Inhibitory Transmitters at Central Synapses

Cited by 236 publications

References 80 publications

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions

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