ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Differential dependence of axo-dendritic and axo-somatic GABAergic synapses on GABAA receptors containing the alpha1 subunit in Purkinje cells.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 89 citations in OpenAlex.
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- Enhancing neuronal chloride extrusion rescues α2/α3 GABANature communications · 2020Article
- Genetic Deletion of GABAFrontiers in cellular neuroscience · 2019Article
- Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction.Frontiers in molecular neuroscience · 2019Article
- GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Regulation of GABAergic synapse development by postsynaptic membrane proteins.Brain research bulletin · 2017Review
- A Comprehensive Optogenetic Pharmacology Toolkit for In Vivo Control of GABA(A) Receptors and Synaptic Inhibition.Neuron · 2015Article
- Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of GABA(A) receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Spontaneous Network Activity and Synaptic Development.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2014Review
- Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Gephyrin: a master regulator of neuronal function?Nature reviews. Neuroscience · 2014Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synapse formation and maintenance require extensive transsynaptic interactions involving multiple signal transduction pathways. In the cerebellum, Purkinje cells (PCs) receive GABAergic, axo-dendritic synapses from stellate cells and axo-somatic synapses from basket cells, both with GABAA receptors containing the alpha1 subunit. Here, we investigated the effects of a targeted deletion of the alpha1 subunit gene on GABAergic synaptogenesis in PCs, using electrophysiology and immunoelectron microscopy. Whole-cell patch-clamp recordings in acute slices revealed that PCs from alpha1(0/0) mice lack spontaneous and evoked IPSCs, demonstrating that assembly of functional GABAA receptors requires the alpha1 subunit. Ultrastructurally, stellate cell synapses on PC dendrites were reduced by 75%, whereas basket cell synapses on the soma were not affected, despite the lack of GABAA-mediated synaptic transmission. Most strikingly, GABAergic terminals were retained in the molecular layer of adult alpha1(0/0) mice and formed heterologous synapses with PC spines characterized by a well differentiated asymmetric postsynaptic density. These synapses lacked presynaptic glutamatergic markers and postsynaptic AMPA-type glutamate receptors but contained delta2-glutamate receptors. During postnatal development, initial steps of GABAergic synapse formation were qualitatively normal, and heterologous synapses appeared in parallel with maturation of dendritic spines. These results suggest that synapse formation in the cerebellum is governed by neurotransmitter-independent mechanisms. However, in the absence of GABAA-mediated transmission, GABAergic terminals in the molecular layer apparently become responsive to synaptogenic signals from PC spines and form stable heterologous synapses. In contrast, maintenance of axo-somatic GABAergic synapses does not depend on functional GABAA receptors, suggesting differential regulation in distinct subcellular compartments.
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