Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS
Open accessAbstract
Group III metabotropic glutamate receptors (mGluRs) are selectively activated by L-2-amino-4-phosphonobutyrate (L-AP4), which produces depression of synaptic transmission. The relative contribution of different group III mGluRs to the effects of L-AP4 remains to be clarified. Here, we assessed the distribution of mGluR4 in the rat and mouse brain using affinity-purified antibodies raised against its entire C-terminal domain. The antibodies reacted specifically with mGluR4 and not with other mGluRs in transfected COS 7 cells. No immunoreactivity was detected in brains of mice with gene-targeted deletion of mGluR4. Pre-embedding immunocytochemistry for light and electron microscopy showed the most intense labelling in the cerebellar cortex, basal ganglia, the sensory relay nuclei of the thalamus, and some hippocampal areas. Immunolabelling was most intense in presynaptic active zones. In the basal ganglia, both the direct and indirect striatal output pathways showed immunolabelled terminals forming mostly type II synapses on dendritic shafts. The localisation of mGluR4 on GABAergic terminals of striatal projection neurones suggests a role as a presynaptic heteroreceptor. In the cerebellar cortex and hippocampus, mGluR4 was also localised in terminals establishing type I synapses, where it probably operates as an autoreceptor. In the hippocampus, mGluR4 labelling was prominent in the dentate molecular layer and CA1-3 strata lacunosum moleculare and oriens. Somatodendritic profiles of some stratum oriens/alveus interneurones were richly decorated with mGluR4-labelled axon terminals making either type I or II synapses. This differential localisation suggests a regulation of synaptic transmission via a target cell-dependent synaptic segregation of mGluR4. Our results demonstrate that, like other group III mGluRs, presynaptic mGluR4 is highly enriched in the active zone of boutons innervating specific classes of neurones. In addition, the question of alternatively spliced mGluR4 isoforms is discussed.
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Group III metabotropic glutamate receptors (mGluR4, mGluR7, and mGluR8) are concentrated in active zones.
“Elegant immuno-EM studies demonstrated that group III metabotropic glutamate receptors (mGluR4, mGluR7, and mGluR8) are concentrated in active zones (Shigemoto et al., 1996; Corti et al., 2002; Kogo et al., 2004; Ferraguti et al., 2005).”
From The Presynaptic Active Zone (2012) · cites this paper as Corti et al., 2002
Our indexed copy contains a bibliographic record identifying a study of mGluR4 synaptic localisation (title and citation record), but no passage reports whether mGluR4, mGluR7, or mGluR8 is concentrated in active zones. Searches for active-zone localisation and for mGluR7 and mGluR8 found no relevant passage. (LLM, conf=0.72)
Experimental — accuracy not yet measuredMetabotropic group III receptors expressed by GABAergic neurons are only enriched in the active zones of synapses formed by these neurons onto other interneurons, but not in synapses onto pyramidal neurons.
“Similarly, metabotropic group III receptors expressed by GABAergic neurons are only enriched in the active zones of synapses formed by these neurons onto other interneurons, but not in synapses onto pyramidal neurons (Corti et al., 2002; Kogo et al., 2004; Ferraguti et al., 2005).”
From The Presynaptic Active Zone (2012) · cites this paper as Corti et al., 2002
The available copy contains a bibliographic record for Corti et al. (2002), including its title and page range (403–420), but no passage addressing receptor localisation at GABAergic synapses. Searches for active zones at interneuron versus pyramidal-neuron synapses and for mGluR4 synaptic localisation returned no matching passages, so the claim cannot be checked against this copy. (LLM, conf=0.75)
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- Authors
- Corti, C., Aldegheri, L., Somogyi, P., & Ferraguti, F.
- Affiliations
- University of Cambridge (GB)
- GlaxoSmithKline (Italy) (IT)
- University of Oxford (GB)
- Corresponding author
- Ferraguti, F
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 110
- Issue
- 3
- Pages
- 403-420
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2024911651
- Cited by
- 243
- References
- 6
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 15 · 2019: 13 · 2018: 9 · 2017: 14 · 2016: 8 · 2015: 10 · 2014: 14 · 2013: 10 · 2012: 21
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- mGluR4, group III mGluRs, autoreceptors, active zone, L-AP4, cerebellar cortex, basal ganglia, striatal projection neurons, hippocampus, interneurons, synaptic transmission regulation, alternative splicing
- MeSH terms
- Animals, Basal Ganglia, Brain, Hippocampus, Immunohistochemistry, Microscopy, Electron, Synaptic Transmission, Synaptic Membranes, Rats, Sprague-Dawley, Presynaptic Terminals, Receptors, Metabotropic Glutamate, Mice, Knockout, COS Cells, Mice, Rats
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