Neuronal activity during development: permissive or instructive?

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Abstract

Experimental studies over the past year have shown that neural activity has a range of effects on the development of neural pathways. Although activity appears unimportant for establishing many aspects of the gross morphology and topology of the brain, there are many cases where the presence of neural activity is essential for the formation of a mature system of neural connections; in some instances, the pattern of neural activity actually orchestrates the final arrangement of neural connections.

Introduction

Some aspects of neural circuit development require neural activity to perform with precision. A classic example is the development of ocular dominance columns in visual cortex, which fail to form in the absence of afferent activity arriving from the eyes 1, 2, 3. What remains uncertain is whether the role of neural activity in development is instructive or permissive. In other words, it is not clear whether the pattern of neural activity molds directly the development of the neural connections or whether it is simply the presence of neural activity that enables other developmental cues, such as molecular factors, to guide appropriate neural connections. This review will examine progress over the past year toward distinguishing between an instructive and a permissive role for neural activity in the development of brain circuits. Recent evidence regarding putative cellular and synaptic mechanisms by which neural activity might influence the development of neural circuits will also be discussed.

Section snippets

How can one distinguish between permissive and instructional roles for activity?

The most direct and informative way to distinguish between instructive and permissive roles for neural activity is to change the pattern or information content of the neural activity, while keeping the overall activity constant, and see whether and how this affects the development of neural circuits. The expectation is that different patterns of afferent activity will ‘teach’ or reinforce a different arrangement of connections, perhaps using a competitive mechanism that executes a form of

Spontaneous neural activity during development

Short of a way to substitute for spontaneous activity with artificially induced stimuli, many experimenters have instead explored the effects of simply interfering with spontaneous activity on the development of neural connections. For instance, spontaneous waves of neural activity in the retina, which are present during the development of the visual pathways even before eye opening 8, 9, were recently shown to be necessary for the formation of eye-specific laminae in the ferret lateral

Neural activity in developmental plasticity

The difficulty with directly interfering in the early development of neural connection patterns (because of the fragility of young animals) has led many researchers to alternative experimental approaches. The most common of these is to induce plasticity in partially developed circuits, and then test the role of activity in mediating developmental plasticity. Whether or not the de novo construction of the pattern of neural connections requires instruction from activity is a different question

The amphibian retino-tectal system

In the amphibian visual system, manipulation and observation of the development of the retino-tectal pathway is relatively simple, and many close analogies with the development of mammalian vision can be inferred. For example, the optic tectum normally receives input directly from the contralateral eye only, but can be induced to receive inputs from an ectopic third eye. The doubly innervated tectum then develops eye-preference domains (a.k.a. ocular dominance ‘stripes’) in an

Mechanisms for activity-dependent neural circuit development

An alternative approach to investigating the role of activity in neural circuit development is to interfere with the cellular mechanisms mediating activity-dependent development, without interfering with the activity itself. Changing the ‘instruction’ by modulating the ‘message’ may provide insights into both the mechanism and the message. The NMDA receptor, for the same reasons that it is implicated in learning and memory processes, is a prominent candidate to mediate activity-dependent

Rodent barrel field experiments

The development of some brain structures, particularly early in the establishment of neural pathways, is not directly regulated by neural activity. For example, procedures in which tetrodotoxin (TTX) is applied to essentially the entire brain cavity early in development have resulted in no gross morphological defects in the development of the forebrain and thalamic structures, even though eye-specific laminae in the geniculate nucleus fail to form [11]. These results and those of other

Conclusions

Neural activity is not required for the development of the adult arrangement of all neural connections in the brain. As discussed here, however, there are many instances in which the presence, and perhaps even the pattern, of neural activity is necessary for the formation of precise neural connections. The diversity of apparent effects of neural activity on brain circuit formation may simply define a continuum. This ranges from one extreme, at which neural activity is not at all necessary for

Acknowledgements

I thank John Maunsell and Pamela Petersen-Crair for helpful comments on 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

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