GABA signalling during development: new data and old questions

Varju, Patricia; Katarova, Zoya; Madarász, Emı́lia; Szabó, Gábor

doi:10.1007/s004410100356

Cited by 125 publications

(110 citation statements)

References 84 publications

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“…GAD is often localized around synaptic vesicles, and this result indicates that GABA is localized in both cytoplasm and vesicles in GABAergic neurons although synapses were not formed. Physiological and biochemical studies have demonstrated that non-vesicular forms of GABA are also secreted via the plasma membrane by the reverse transporter action of GABA transporters (GATs) [4,7,9,25,30,63,64,68]. Taken together, in the developing brain, GABA may be non-synaptically released from Golgi cells via the plasma membrane by vesicular and non-vesicular mechanisms.…”

Section: Developmental Changes In the Gaba-releasing Mechanismmentioning

confidence: 99%

“…Taken together, in the developing brain, GABA may be non-synaptically released from Golgi cells via the plasma membrane by vesicular and non-vesicular mechanisms. Non-synaptically released GABA activates GABA A receptors, and plays various roles in brain development [5,6,8,10,33,53,68,74]. At the mature stage, in contrast, GABA is synthesized mainly around axon terminals (Fig.…”

Section: Developmental Changes In the Gaba-releasing Mechanismmentioning

confidence: 99%

“…At the mature stage, in contrast, GABA is synthesized mainly around axon terminals (Fig. 9D), transported into synaptic vesicles, and released at the synaptic site [21,44,45,56,68]. Synaptically released GABA activates GABA A receptors, including the α1 and α6 subunits, on the postsynaptic membrane, mediates inhibitory synaptic transmission, and regulates glutamatergic excitability activity [33,42,52,53].…”

Section: Developmental Changes In the Gaba-releasing Mechanismmentioning

confidence: 99%

“…Recent studies have revealed that GABAergic signaling changes developmentally. In the immature CNS, GABA serves as an excitatory transmitter, and acts as a trophic factor for development, such as changes in cell proliferation, cell migration, axonal growth, synapse formation, steroid-mediated sexual differentiation and cell death [5,8,10,33,43,53,68]. Nevertheless, it is still unclear how GABA exerts its effect on neurons, and how functional GABAergic synapses are established.…”

Section: Introductionmentioning

confidence: 99%

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Morphological development and maturation of the GABAergic synapses in the mouse cerebellar granular layer

Takayama¹,

Inoue²

2004

Developmental Brain Research

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In the adult central nervous system (CNS), γ-amino butyric acid (GABA) is a predominant inhibitory neurotransmitter, which regulates glutamatergic activity. Recent studies have revealed that GABA serves as an excitatory transmitter in the immature CNS, and is involved in brain morphogenesis. To elucidate how GABA exerts its effect on immature neurons and how GABAergic synapses are formed, we examined both development of pre-and post-synaptic elements of the GABAergic synapses formed between granule and Golgi cells in the mouse cerebellar granular layer. Immunohistochemistry for glutamic acid decarboxylase (GAD) demonstrated that GABA was localized throughout the Golgi cells before postnatal day 7 (P7), and became confined to the axon terminals during the second postnatal week. Electron microscopic analysis demonstrated that GABAergic synapses were clearly detected at P10. In situ hybridization and immunohistochemistry for the GABA A receptor α1 and α6 subunits, which are mainly involved in inhibitory synaptic transmission, demonstrated that both subunits appeared at P7. Distribution of both subunits expanded in the granular layer with special reference to the development of GABAergic synapses.Furthermore, the majority of the subunits accumulated adjacent to the GABAergic terminals.These results suggested that in the granular layer, GABA might be non-synaptically secreted from Golgi cell axons and dendrites during the first postnatal week. From the second postnatal week, GABA is synaptically released and begins to mediate inhibitory transmission.Furthermore, it was suggested that GABAergic innervation could initiate expression and trafficking of the GABA A receptors containing the α1 and α6 subunits.

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Section: Developmental Changes In the Gaba-releasing Mechanismmentioning

confidence: 99%

Section: Developmental Changes In the Gaba-releasing Mechanismmentioning

confidence: 99%

Section: Developmental Changes In the Gaba-releasing Mechanismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Morphological development and maturation of the GABAergic synapses in the mouse cerebellar granular layer

Takayama¹,

Inoue²

2004

Developmental Brain Research

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“…Moreover, maturation of other neurons may be disturbed in the central cerebellar mass. Early in cerebellar development, α2 and α3 subunits are abundantly expressed [2,3,4,5,29,53,63]. Upon maturation, expression of the α2 and α3 subunits decrease dramatically and the α1 and α6 subunits start to be expressed in the cerebellum [29].…”

Section: Regulatory Mechanisms Underlying the Expression Of The Gamentioning

confidence: 99%

Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum

Takayama

Inoue

2003

Developmental Brain Research

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Synaptic transmission mediated by γ-amino butyric acid (GABA) plays an important role in inhibition of glutamatergic excitatory transmission and expression of higher brain functions, such as memory, learning and anxiety. To elucidate mechanisms underlying formation of the postsynaptic elements for GABAergic transmission, we employed the reeler mutant mice in this study. In the reeler cerebellum, abnormal cytoarchitecture and an aberrant environment affect the formation of neural networks and maturation of neurons. We examined the expression and localization of GABA A receptor α subunits in the reeler cerebellum and determined whether various abnormalities in the reeler mice affected formation of the postsynaptic elements. In situ hybridization analysis revealed that the specific expression of α subunit mRNAs in each neuronal type was preserved. Abnormal expression of α subunits was not detected, although GABAergic networks were altered and neuronal maturation was severely disturbed. Immunohistochemistry for the α1 and α6 subunits, which were expressed abundantly in the reeler cerebellum, revealed that both subunit-proteins accumulated at positions adjacent to GABAergic terminals. These results, taken together, suggested that expression of the GABA A receptor subunits in postsynaptic neurons might be genetically determined, but trafficking and accumulation of the subunit proteins at the GABAergic synapse may be induced by GABAergic innervation. Classification Terms

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Impact of Ethanol on the Developing GABAergic System

Isayama

Leite

Lima

et al. 2009

The Anatomical Record

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Alcohol intake during pregnancy has a tremendous impact on the developing brain. Embryonic and early postnatal alcohol exposures have been investigated experimentally to elucidate the fetal alcohol spectrum disorders' (FASD) milieu, and new data have emerged to support a devastating effect on the GABAergic system in the adult and developing nervous system. GABA is a predominantly inhibitory neurotransmitter that during development excites neurons and orchestrates several developmental processes such as proliferation, migration, differentiation, and synaptogenesis. This review summarizes and brings new data on neurodevelopmental aspects of the GABAergic system with FASD in experimental telencephalic models. Anat Rec, 292:1922Rec, 292: -1939Rec, 292: , 2009. Key words: GABA; developing brain; prenatal ethanol exposure; cortical neurons; ganglionic eminence THE DEVELOPING TELENCEPHALONThe central nervous system develops in a programmed order, following subsequent steps. Because of the cellular diversity and complexity throughout its laminar and areal structure, the cerebral cortex is a good model for studying developmental events. After closure of the neural tube, progenitor cells located near its lumen (ventricular zones) start to proliferate intensely, first to increase progenitor pool and then to originate postmitotic cells (Rakic, 1988). The destination of proliferating cells is largely influenced by their mitotic spindle rotation during metaphase and their cleavage plane during Abbreviations used: ARBD ¼ alcohol-related birth defects; ARND ¼ alcohol-related neurodevelopmental disorders; BDNF ¼ brain-derived neurotrophic factor; BrdU ¼ bromodeoxyuridine;

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GABA signalling during development: new data and old questions

Cited by 125 publications

References 84 publications

Morphological development and maturation of the GABAergic synapses in the mouse cerebellar granular layer

Morphological development and maturation of the GABAergic synapses in the mouse cerebellar granular layer

Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum

Impact of Ethanol on the Developing GABAergic System

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