Neuronal replacement in adult brain

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Abstract

The discovery of spontaneous neuronal replacement in the adult vertebrate brain has changed the way in which we think about the biology of memory. This is because neuronal replacement is likely to have an impact on what a brain remembers and what it learns. Neuronal replacement has also changed the way in which we go about exploring new strategies for brain repair. Our new outlook on both these matters is all the more remarkable because of the pervasiveness of the earlier dogma, which for warm-blooded vertebrates relegated neurogenesis to embryonic development and, for a few neuronal classes, early postnatal life. The discovery of constant neuronal replacement in the adult brain was remarkable, too, in that it was not required by what we thought to be the logic of nervous system function. Moreover, no previous facts prepared us for it. Much of the modern theory of learning embraced the view of modifiable synapses as the key players in learning and as the repositories of memory. But if this were so, what would be the point of neuronal replacement in healthy brain tissue? In what follows, I will briefly review the work of Joseph Altman, because he was the first one to challenge the notion that new neurons were not produced in adulthood. I will then review what we know about neuronal replacement in the song system of birds, which my laboratory has studied for many years. In closing, I will offer a general theory of long-term memory that, if true, might explain why adult nervous systems constantly replace some of their neurons.

Section snippets

First reports of adult neurogenesis in mammals

In 1962 Joseph Altman [1] published in Science a report entitled “Are New Neurons Formed in the Brains of Adult Mammals?” He used an insulated hypodermic needle to make an electrolytic lesion in the lateral geniculate body of young adult rats. The same needle was used to inject the cell birth marker 3H-thymidine into the lesioned area. These animals were killed 1 day to several months later. Autoradiographic treatment of brain sections revealed 3H-labeled cells identified as neurons in the

Setting the stage

Adult neurogenesis and neuronal replacement are two different phenomena. Clearly, for the latter to happen, the former must too, in which case neurogenesis is part of a replacement program. However, there can be adult neurogenesis without neuronal replacement, as in the instances of sustained CNS growth discussed in the previous section. The story I would like to tell focuses on adult neuronal replacement, though it did not start that way. It started with a study of vocal learning in birds.

In

New neuron recruitment during song ontogeny suggests relation between innate developmental program and experience

Recent work by Wilbrecht et al. [78] suggests a more complex situation. These authors denervated one side of the syrinx of 26-day-old juvenile zebra finches. The nerve section silenced the ipsilateral syringeal half, but the operated birds were still able to imitate a tutor song with the contralateral side, though the imitation was not as close as it might normally be. The authors looked at overall HVC neuron numbers during vocal ontogeny and after its end and documented new neuron recruitment

Similarities and differences between birds and mammals: three caveats and some reflections on terminology

Most of this review focused on the songbird brain because much of the early work that established the occurrence and mechanisms of spontaneous neuronal replacement in the adult vertebrate brain was done with this material, which I know well. Possibly, some of the insights gleaned from the avian brain will apply to all vertebrates, including mammals, even if adult birds and mammals differ in the presence of radial glia, in the kinds of neurons normally born in adulthood, and in the extent to

Why neuronal replacement?

Now, a simple question. Why neuronal replacement? Surely, this is the basic conceptual issue. It seems unlikely that this trait evolved to help animals recover from brain infirmity or lesion. Animals in nature, unprotected by a caring society, may seldom have the time to recover from brain dysfunction. It also seems unlikely that neuronal replacement evolved as a response to normal wear and tear (except perhaps in the olfactory epithelium?), because in terms of neuronal classes and circuits, it

Adult neurogenesis as a tool for brain repair

Until the relatively recent, broad based surge of interest in adult neurogenesis, which started in the mid 1980s [57], grafts of embryonic brain tissue seemed to be the only tool for inducing circuit repair (e.g., [17]). Grafts still remain a strong tool, but it would seem more elegant to induce the brain to use its own neurogenic potential to replace lost cells. These two approaches are likely to vie for primacy, and it may be that there are special conditions or parts of the brain that will

The balance between optimism and pessimism

The songbird brain offers the strongest example of adult neurogenesis, because new neurons are added to so many parts of the telencephalon [57]. Yet even in this case, if one were to take the song system as an example, spontaneous neuronal replacement occurs in only 5% or less of the types of neurons present in adulthood. That is to say, the great majority of neurons are not normally replaced. The percent of neuron types that is affected by spontaneous replacement is even lower in the mammalian

Societal considerations

The discovery of neurogenesis and neuronal replacement in brains that have ceased to grow is likely to affect the way in which we think about long-term memory and the natural limits on learning. An understanding of the latter might affect the way in which adults are taught. This is not a small matter when many adults get to live relatively long lives and often find it necessary to change careers or take refresher courses.

Postnatal or adult neurogenesis and neuronal replacement may also play a

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