Orchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice

doi:10.1016/j.tins.2004.05.003

Trends in Neurosciences

Volume 27, Issue 7, 1 July 2004, Pages 415-421

https://doi.org/10.1016/j.tins.2004.05.003 Get rights and content

Abstract

Appropriate specification of neurotransmitters is a key feature of neuronal network assembly. There is much evidence that genetic programs are responsible for this aspect of cell fate and neuronal differentiation. Are there additional ways in which these processes are shaped? Recent findings demonstrate that altering patterned Ca²⁺ spike activity that is spontaneously generated by different classes of embryonic spinal neurons in vivo changes expression of neurotransmitters in a homeostatic manner, as if to achieve a constant level of excitation. Activity-dependent changes in presynaptic transmitter expression pose a matching problem: are there corresponding changes in postsynaptic transmitter receptor expression, or are axons rerouted to novel targets with which functional synapses can be formed?

Section snippets

Control of transmitter phenotype by Ca²⁺ signaling

Several studies have suggested that transmitter specification is regulated by Ca²⁺ signaling. Depolarization or neuronal activity generating Ca²⁺ influx stimulates adrenergic differentiation of cultured superior cervical ganglion neurons, by suppressing cholinergic differentiation in response to a factor in conditioned medium; blocking influx leads to an increased incidence of cholinergic neurons [3]. Suppressing elevation of Ca²⁺ levels in cultured hypothalamic neurons also enhances expression

Roles of transcription factors

Regulation of neurotransmitter expression by transcription factors has been extensively investigated, and neurotransmitter phenotypes are altered when genes encoding transcription factors are either knocked out or ectopically expressed. For example, misexpression of homeobox genes MNR2 or Lhx3/Isl1 in the embryonic chick spinal cord drives inappropriate expression of the motor neuron transmitter ACh in interneurons 13, 14 (Figure 3). Loss-of-function and gain-of-function studies show that

Roles of signaling proteins

Signaling proteins are also involved in the specification of transmitters. In several cases these signaling proteins promote production of transcription factors that lead to the initial expression of transmitters. Bone morphogenetic proteins (BMPs) regulate expression of Mash1 and Phox2 genes in zebrafish, rat and chick that lead to expression of tyrosine hydroxylase, dopamine-β-hydroxylase and the noradrenergic phenotype 19, 22, 33 (Figure 4). Specification of neurons producing dopamine and

Discussion

Patterns of Ca²⁺ spike activity emerge as central to the normal expression of transmitters in the neural tube of Xenopus embryos. Decreasing or increasing this activity alters transmitter expression. Particular patterns of spike activity might also be adequate to specify particular transmitters; in vitro imposition of patterns that most closely resemble in vivo patterns is most successful in achieving the in vivo transmitter phenotype. These results are unlikely to be due to the birth and death

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Trends in Neurosciences

Orchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice

Abstract

Section snippets

Control of transmitter phenotype by Ca2+ signaling

Roles of transcription factors

Roles of signaling proteins

Discussion

Mol. Cell. Neurosci.

Cell

Cell

Neuron

Neuron

Neuron

Neuron

Mol. Cell. Neurosci.

Neuron

Neuron

Cell

Dev. Biol.

Neuron

Neuron

Neuron

Curr. Opin. Neurobiol.

Neuron

Mol. Cell. Neurosci.

Halocynthia roretzi. Dev. Biol.

Neuroscience

Dev. Biol.

Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors

EMBO J.

GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro

Development

On the role of Ca2+ in the transmitter choice made by cultured sympathetic neurons

J. Neurosci.

Calcium-dependent regulation of cholinergic cell phenotype in the hypothalamus in vitro

J. Neurophysiol.

Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca2+ transients

Nature

Local and global spontaneous calcium events regulate neurite outgrowth and onset of GABAergic phenotype during neural precursor differentiation

J. Neurosci.

Neuronal activity and neurotrophic factors regulate GAD-65/67 mRNA and protein expression in organotypic cultures of rat visual cortex

Eur. J. Neurosci.

Orchestrating neuronal differentiation: patterns of Ca²⁺ spikes specify transmitter choice

Control of transmitter phenotype by Ca²⁺ signaling

On the role of Ca²⁺ in the transmitter choice made by cultured sympathetic neurons

Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca²⁺ transients