Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction
The diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00154/full |
| _version_ | 1818174182587891712 |
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| author | April Contreras Dustin J. Hines Rochelle M. Hines |
| author_facet | April Contreras Dustin J. Hines Rochelle M. Hines |
| author_sort | April Contreras |
| collection | DOAJ |
| description | The diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon initial segment (AIS). Here, we review and examine the cellular and molecular regulation of soma and axon targeting GABAergic synapses in the cortex and hippocampus. We also describe their role in controlling network activity in normal and pathological states. Recent studies have demonstrated a specific role for postsynaptic dystroglycan in the formation and maintenance of cholecystokinin positive basket cell terminals contacting the soma, and postsynaptic collybistin in parvalbumin positive chandelier cell contacts onto the AIS. Unique presynaptic molecular contributors, LGI2 and FGF13, expressed in parvalbumin positive basket cells and chandelier cells, respectively, have also recently been identified. Mutations in the genes encoding proteins critical for somatic and AIS inhibitory synapses have been associated with human disorders of the nervous system. Dystroglycan dysfunction in some congenital muscular dystrophies is associated with developmental brain malformations, intellectual disability, and rare epilepsy. Collybistin dysfunction has been linked to hyperekplexia, epilepsy, intellectual disability, and developmental disorders. Both LGI2 and FGF13 mutations are implicated in syndromes with epilepsy as a component. Advancing our understanding of the powerful roles of somatic and axonic GABAergic contacts in controlling activity patterns in the cortex and hippocampus will provide insight into the pathogenesis of epilepsy and other nervous system disorders. |
| first_indexed | 2024-12-11T19:40:20Z |
| format | Article |
| id | doaj.art-07ff00820ae04360985499b617a3db1b |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-11T19:40:20Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-07ff00820ae04360985499b617a3db1b2022-12-22T00:53:01ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-06-011210.3389/fnmol.2019.00154463002Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and DysfunctionApril ContrerasDustin J. HinesRochelle M. HinesThe diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon initial segment (AIS). Here, we review and examine the cellular and molecular regulation of soma and axon targeting GABAergic synapses in the cortex and hippocampus. We also describe their role in controlling network activity in normal and pathological states. Recent studies have demonstrated a specific role for postsynaptic dystroglycan in the formation and maintenance of cholecystokinin positive basket cell terminals contacting the soma, and postsynaptic collybistin in parvalbumin positive chandelier cell contacts onto the AIS. Unique presynaptic molecular contributors, LGI2 and FGF13, expressed in parvalbumin positive basket cells and chandelier cells, respectively, have also recently been identified. Mutations in the genes encoding proteins critical for somatic and AIS inhibitory synapses have been associated with human disorders of the nervous system. Dystroglycan dysfunction in some congenital muscular dystrophies is associated with developmental brain malformations, intellectual disability, and rare epilepsy. Collybistin dysfunction has been linked to hyperekplexia, epilepsy, intellectual disability, and developmental disorders. Both LGI2 and FGF13 mutations are implicated in syndromes with epilepsy as a component. Advancing our understanding of the powerful roles of somatic and axonic GABAergic contacts in controlling activity patterns in the cortex and hippocampus will provide insight into the pathogenesis of epilepsy and other nervous system disorders.https://www.frontiersin.org/article/10.3389/fnmol.2019.00154/fullGABAergic synapse developmentepilepsies and epileptic syndromescholecystokininparvalbumininterneuronGABAA receptor subunits |
| spellingShingle | April Contreras Dustin J. Hines Rochelle M. Hines Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction Frontiers in Molecular Neuroscience GABAergic synapse development epilepsies and epileptic syndromes cholecystokinin parvalbumin interneuron GABAA receptor subunits |
| title | Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction |
| title_full | Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction |
| title_fullStr | Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction |
| title_full_unstemmed | Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction |
| title_short | Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction |
| title_sort | molecular specialization of gabaergic synapses on the soma and axon in cortical and hippocampal circuit function and dysfunction |
| topic | GABAergic synapse development epilepsies and epileptic syndromes cholecystokinin parvalbumin interneuron GABAA receptor subunits |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00154/full |
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