The origin of spontaneous activity in developing networks of the vertebrate nervous system

https://doi.org/10.1016/S0959-4388(99)80012-9Get rights and content

Abstract

Spontaneous neuronal activity has been detected in many parts of the developing vertebrate nervous system. Recent studies suggest that this activity depends on properties that are probably shared by all developing networks. Of particular importance is the high excitability of recurrently connected, developing networks and the presence of activity-induced transient depression of network excitability. In the spinal cord, it has been proposed that the interaction of these properties gives rise to spontaneous, periodic activity.

Introduction

Research over the past 10 years has established that spontaneous activity is a characteristic feature of developing neuronal networks. This work has been performed in various parts of the nervous system, in a wide variety of species and at several different developmental stages. Despite the diversity of these investigations, several general principles are beginning to emerge concerning the genesis of spontaneous activity by developing networks. In this review, I will discuss these principles in the context of the activity produced by developing synaptic networks in the vertebrate nervous system. An important distinction — and one that is often not made — is between the activity generated before and after the formation of chemical synaptic networks; many publications confuse the two phenomena, which are generated by different mechanisms and probably subserve quite different developmental functions.

The earliest studies of activity in the developing nervous system involved observations of embryonic motility. Such observations had been made for at least 300 years, and many of them were collected and described by Preyer in his monograph published in 1885 (and reprinted in English in 1937 [1]). In this monograph, he describes embryonic movements in an extraordinary diversity of species, including invertebrates, fishes, amphibians, reptiles, birds and mammals. Modern research on embryonic motility was inaugurated by Hamburger and his colleagues 2, 3, who studied the development of embryonic movements in the chick, supplementing observation with electromyography and electrophysiology. These early studies identified two features of embryonic motility that have been found to characterize spontaneous activity in all parts of the developing nervous system examined so far. First, the activity is restricted to a particular period of development and, secondly, it is organized into bouts or episodes separated by periods of quiescence. To understand the genesis of this activity, several conditions need to be fulfilled. First, it is essential to identify which neuron classes generate the activity and which members of the network are output elements. Second, it is necessary to establish what initiates and terminates the activity. Finally, the factors determining the organization of the activity in space and time must be identified.

I will describe progress in understanding these mechanisms in three parts of the nervous system that have been studied the most extensively: the spinal cord, the hippocampus and the retina. Spontaneous activity has been recorded from several other regions, but its mechanisms have not been addressed systematically 4, 5, 6, 7, 8, 9. The activity produced by cultured cortical neurons has also been studied and bears many similarities to developing network activity, but will not be covered here as it has recently been discussed elsewhere [10].

Section snippets

Distinct types of spontaneous activity are produced before and after the development of chemical synaptic networks

Activity produced by the early nervous system, before the formation of synaptic networks, comprises calcium transients that are coordinated in groups of cells coupled by gap junctions. This type of activity has been observed in the early mammalian cortex 11, 12, the avian retina [13] and the amphibian neural tube (for a review, see [14]). Cells of the amphibian neural tube express two types of calcium transient that have been denoted ‘spikes and waves’ [14]. Spikes rise rapidly and decay over

Mechanisms of network-driven spontaneous activity

Once chemical synaptic networks form, a new type of activity emerges that I will refer to as network-driven activity. It is abolished by tetrodoxin (TTX) or by antagonists of chemical synaptic transmission, and it involves the synchronous activation of many, if not all, members of a particular network through their synaptic interactions. In what follows, I will describe the activity produced in several regions of the nervous system and discuss what is known about the mechanism of its genesis. I

Common mechanisms may operate in the production of spontaneous activity by diverse, developing networks

One striking conclusion to emerge from the work I have discussed above is that common mechanisms may operate in the activation of networks as diverse as the retina and spinal cord. In many systems, spontaneous activity appears to be generated by network interactions — in particular, positive feedback excitation in a recurrently connected, excitatory network. The precise mechanisms for termination of this activity, and the factors that control the duration of quiescent periods, are not fully

Conclusions

Accumulating evidence suggests that the high excitability of developing networks coupled with some form of transient, activity-dependent network depression underlies the genesis of spontaneous activity by synaptically coupled networks. It also seems likely that the mechanisms responsible for spontaneous activity will be intimately connected with those regulating synaptic efficacy during development. A major challenge for the future will be to disentangle these two aspects of network development

Acknowledgements

Particular thanks to Rachel Wong and Michael Weliky for discussing published and unpublished work. Special thanks to Evelyne Sernagor for providing the unpublished data illustrated in Figure 3d. Thanks are also due to Uri Cohen, Patrick Whelan, Joel Tabak, Nikolai Chub and Agnes Bonnot for their comments on earlier versions of the manuscript.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

References (75)

  • M Barry et al.

    The effects of excitatory amino acids and their antagonists on the generation of motor activity in the isolated chick cord

    Dev Brain Res

    (1987)
  • A Rao et al.

    Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons

    Neuron

    (1997)
  • AM Craig

    Activity and synaptic receptor targeting: the long view

    Neuron

    (1998)
  • GW Davis et al.

    Genetic analysis of synaptic development and plasticity: homeostatic regulation of synaptic efficacy

    Curr Opin Neurobiol

    (1998)
  • GW Davis et al.

    Postsynaptic PKA controls quantal size and reveals a retrograde signal that regulates presynaptic transmitter release in Drosophila

    Neuron

    (1998)
  • LC Rutherford et al.

    BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses

    Neuron

    (1998)
  • KW Roche et al.

    Glutamate receptor phosphorylation and synaptic plasticity

    Curr Opin Neurobiol

    (1994)
  • LM De La Prida et al.

    Analytical characterization of spontaneous activity evolution during hippocampal development in the rabbit

    Neurosci Lett

    (1996)
  • A Luthi et al.

    H-current: properties of a neuronal and network pacemaker

    Neuron

    (1998)
  • E Sernagor et al.

    Influence of spontaneous activity and visual experience on developing retinal receptive fields

    Curr Biol

    (1996)
  • MB Feller et al.

    Dynamic properties shape spatiotemporal properties of retinal waves

    Neuron

    (1997)
  • R Mooney et al.

    Thalamic relay of spontaneous retinal activity prior to vision

    Neuron

    (1996)
  • Preyer W: Embryonic motility and sensitivity. Translated from the original German text by Goghill GE and Legner WK....
  • V Hamburger

    The developmental history of the motor neuron

    Neurosci Res Prog Bull

    (1976)
  • A Bekoff et al.

    Coordinated motor output in the hindlimb of the 7-day-old chick embryo

    Proc Natl Acad Sci USA

    (1975)
  • WR Lippe

    Rhythmic spontaneous activity in the developing avian auditory system

    J Neurosci

    (1994)
  • AW Gummer et al.

    Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii)

    Neuroreport

    (1994)
  • MJ Christie et al.

    Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats

    J Neurosci

    (1989)
  • G Fortin et al.

    Rhythm generation in the segmented hindbrain of chick embryos

    J Physiol

    (1995)
  • SK Itaya et al.

    Evolution of spontaneous activity in the rat developing superior colliculus

    Can J Pharmacol

    (1994)
  • JJ Greer et al.

    Respiratory and locomotor patterns generated in the fetal rat brain stem-spinal cord in vitro

    J Neurophysiol

    (1992)
  • E Maeda et al.

    The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons

    J Neurosci

    (1995)
  • R Yuste et al.

    Neuronal domains in developing neocortex

    Science

    (1992)
  • M Catsicas et al.

    Spontaneous Ca2+ transients and their transmission in the developing chick retina

    Curr Biol

    (1998)
  • X Gu et al.

    Breaking the code: regulation of neuronal differentiation by spontaneous calcium transients

    Dev Neurosci

    (1997)
  • K Kandler et al.

    Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication

    J Neurosci

    (1998)
  • LT Landmesser et al.

    Activation patterns of embryonic chick hindlimb muscles recorded in-ovo and in an isolated spinal cord preparation

    J Physiol

    (1984)
  • Cited by (339)

    • KCC2 is a hub protein that balances excitation and inhibition

      2020, Neuronal Chloride Transporters in Health and Disease
    View all citing articles on Scopus
    View full text