Glutamate and GABA receptor signalling in the developing brain

doi:10.1016/j.neuroscience.2004.09.042

Neuroscience

Volume 130, Issue 3, 2005, Pages 567-580

https://doi.org/10.1016/j.neuroscience.2004.09.042 Get rights and content

Abstract

Our understanding of the role played by neurotransmitter receptors in the developing brain has advanced in recent years. The major excitatory and inhibitory neurotransmitters in the brain, glutamate and GABA, activate both ionotropic (ligand-gated ion channels) and metabotropic (G protein-coupled) receptors, and are generally associated with neuronal communication in the mature brain. However, before the emergence of their role in neurotransmission in adulthood, they also act to influence earlier developmental events, some of which occur prior to synapse formation: such as proliferation, migration, differentiation or survival processes during neural development. To fulfill these actions in the constructing of the nervous system, different types of glutamate and GABA receptors need to be expressed both at the right time and at the right place. The identification by molecular cloning of 16 ionotropic glutamate receptor subunits, eight metabotropic glutamate receptor subtypes, 21 ionotropic and two metabotropic GABA receptor subunits, some of which exist in alternatively splice variants, has enriched our appreciation of how molecular diversity leads to functional diversity in the brain. It now appears that many different types of glutamate and GABA receptor subunits have prominent expression in the embryonic and/or postnatal brain, whereas others are mainly present in the adult brain. Although the significance of this differential expression of subunits is not fully understood, it appears that the change in subunit composition is essential for normal development in particular brain regions. This review focuses on emerging information relating to the expression and role of glutamatergic and GABAergic neurotransmitter receptors during prenatal and postnatal development.

Section snippets

Developmental expression of neurotransmitter receptor subunits

One indicator of the functional importance of neurotransmitter receptor subunit diversity comes from examining the subunit mRNA or protein changes seen during development. Although the exact changes in subunit expression vary with brain region, it now appears that many different types of neurotransmitter receptors are present in the embryonic brain, while others are dominant in the postnatal brain or in the adult brain.

Neurotransmitter receptor signaling in cell proliferation

Proliferation of neuronal progenitors is one of the fundamental developmental processes responsible for generating the correct number of cells of each type in the correct sequence in the brain. Both cell-intrinsic and -extrinsic factors contribute to changes in cell production and affect cerebral cortical growth. Among other extracellular molecules, neurotransmitter receptors have been implicated in the extrinsic regulation of cell proliferation in the developing telencephalon (see review by

Involvement of neurotransmitter receptor in neuronal migration

After division, most cortical neurons migrate from their site of origin to their final destination in the cerebral cortex. This neuronal movement is essential for the establishment of normal brain organization (see for instance Hatten, 1999). In the developing cerebral cortex, glutamatergic projecting neurons are primarily generated in the VZ and then move to the developing cortical plate (CP) by means of “radial migration” (see review by Marín and Rubenstein, 2001). Most GABAergic

Role of neurotransmitter receptors in early neuronal differentiation

In addition to proliferation and migration, several aspects of neuronal differentiation appears to be regulated by early glutamate- and GABA-mediated signaling. For instance, one of the most important cell types during early cortical neuronal differentiation are the Cajal-Retzius (CR) cells. Among the earliest generated population of neurons in the developing neocortex, CR cells have been implicated in regulating cortical lamination. In rodents, CR cells are transient, being present only up to

Neurotransmitter receptor signaling during synaptogenesis

The establishment of neural networks begins with growing axons recognizing their postsynaptic targets, thus forming synaptic contacts. This process can be divided into two separate phases: the first one (synapse formation) comprises the establishment of functional synaptic communication, and the second phase (synapse maturation) comprises the functional and morphological differentiation of synapses; both phases requiring tight communication between pre- and postsynaptic elements. How specific

Acquisition and localization of neurotransmitter receptors at synapses

A critical aspect in the development of glutamatergic and GABAergic synapses is the progressive recruitment and subsequent accumulation of neurotransmitter receptors at their functional site. Such processes are important, because proper function of synaptic transmission at any given synapse, depends on adequate placement of neurotransmitter receptors of the appropriate number and type, in the neuronal membrane. The differential regulation of the distinct subunits during pre- and postnatal

Concluding remarks

A combination of electrophysiological, molecular, in situ hybridization and immunohistochemical techniques has begun to shed light on the role and distribution of neurotransmitter receptors in the developing brain. This review illuminates recent evidence showing how glutamate and GABA receptors exert different roles during primary nervous structure establishment prior to the emergence of their role in neurotransmission. In this way, the early activation of glutamate and GABA receptor subunits,

Acknowledgments

The authors are grateful to Diane Latawiec, MSc, for the English revision of the manuscript. This work was supported by grants from the Consejería de Sanidad of the Junta de Comunidades de Castilla-La Mancha.

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ReviewGlutamate and GABA receptor signalling in the developing brain

Abstract

Section snippets

Developmental expression of neurotransmitter receptor subunits

Neurotransmitter receptor signaling in cell proliferation

Involvement of neurotransmitter receptor in neuronal migration

Role of neurotransmitter receptors in early neuronal differentiation

Neurotransmitter receptor signaling during synaptogenesis

Acquisition and localization of neurotransmitter receptors at synapses

Concluding remarks

Acknowledgments

Neurosci Lett

Int J Dev Neurosci

Neurosci Lett

Trends Neurosci

Neuroscience

Neuroscience

Mol Cell Neurosci

Brain Res Brain Res Rev

Neuron

Brain Res Dev Brain Res

Curr Opin Neurobiol

Mol Cell Neurosci

Neuron

Brain Res Dev Brain Res

Trends Neurosci

Curr Opin Neurobiol

Neuroscience

Neuron

J Chem Neuroanat

Neuroscience

Neuron

Neuron

Int J Dev Neurosci

Prog Neurobiol

Neuron

Trends Neurosci

Autoradiographic and histological studies of postnatal neurogenesis: IV

Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol

Kainate receptor gene expression in the developing rat brain

J Neurosci

Modulation of intracellular calcium in early neural cells by non-NMDA ionotropic glutamate receptors

Perspect Dev Neurobiol

GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms

J Neurosci

Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus

J Neurosci

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration

J Neurosci

GABA receptor antagonists modulate postmitotic cell migration in slice cultures of embryonic rat cortex

Cereb Cortex

GABA(B) receptors mediate motility signals for migrating embryonic cortical cells

Cereb Cortex

Excitatory actions of GABA during development: the nature of the nurture

Nat Rev Neurosci

Prenatal and postnatal contents of amino acid neurotransmitters in mouse parietal cortex

Dev Neurosci

Localization and stabilization of ionotropic glutamate receptors at synapses

Cell Mol Life Sci

International Union of Pharmacology: XXXIII

Mammalian γ-aminobutyric acidB receptors: structure and function. Pharmacol Rev

Distribution and developmental regulation of metabotropic glutamate receptor 7a in rat brain

J Neurochem

Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus

J Neurosci

Regulation of neurogenesis by growth factors and neurotransmitters

J Neurobiol

Expression and coupling to polyphosphoinositide hydrolysis of group I metabotropic glutamate receptors in early postnatal and adult rat brain

Eur J Neurosci

The developing synapse: construction and modulation of synaptic structures and circuits

Science

Pharmacology and functions of metabotropic glutamate receptors

Annu Rev Pharmacol Toxicol

Phenotypic consequences of deletion of the gamma 3, alpha 5, or beta 3 subunit of the type A gamma-aminobutyric acid receptor in mice

Proc Natl Acad Sci USA

The presence of mGluR7a in the presynaptic active zones of GABAergic and non-GABAergic terminals on interneurones in the rat somatosensory cortex

Cereb Cortex

Distribution of kainate receptor subunits at hippocampal mossy fiber synapses

J Neurosci

Developmental expression of the group III metabotropic glutamate receptor mGluR4a in the medial nucleus of the trapezoid body of the rat

Review
Glutamate and GABA receptor signalling in the developing brain

Mammalian γ-aminobutyric acid_B receptors: structure and function. Pharmacol Rev