In comparing strategies used to control neuron number, we find it useful to view nervous system development as occurring in three phases. The phases overlap--each is a process, not an event. The first phase is the development of a genetic nervous system. This is a nervous system of simple genetic intention, not a blueprint or pile of bricks. Its characteristics are abstract: How many neurons in this stem cell destined to produce, which cells are programmed to die, how much target does this cell need to survive. At the level of the individual, the genetic nervous system is essentially fixed, but over generations it is fluid. As this genetic intent interacts within a world of cells, a real brain appears. A new set of rules only tacitly present in the genome is expressed--the embryonic nervous system emerges. The interaction of its parts defines the shape and size of the nervous system. Neuron numbers are adjusted interactively by changes in proliferative potential and the severity of cell death. Cell fates are established in part through interactions with other cells and with hormones. Glial cell numbers are adjusted to match the neuron populations. This phase of brain development is what the embryologist sees under the microscope. The third and final phase of development begins when the brain starts to function and the animal starts to deal with its world. Small changes in neuron number may occur during this period, but these changes are generally of minor functional importance. At this point, the smaller elements of neuronal organization are refined in shape, number, and distribution. Axons are lost or rearranged; dendrites grow, branch, and retract; synapses are fine-tuned; and finally, receptor densities and transmitter titres are adjusted. Some of these interactions and numerical adjustments continue until the animal dies.

The control of neuron number.

While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of 4 different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora), Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble.

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Coordinated scaling of cortical and cerebellar numbers of neurons.

Control of cell number in the developing mammalian visual system.

To examine the influence of acoustic experience on the development of the mammalian auditory brain stem, darkly pigmented ferrets were reared with a plug inserted in the right outer ear. The plugs were first inserted on postnatal day 23-34 and produced a variable, frequency-dependent attenuation of up to 60 dB. Between 3-15 months after the ear plug was begun, animals were prepared for physiological recording and injection of wheat germ agglutinin-HRP (WGA-HRP) in the left inferior colliculus (IC). The plug was removed and the condition of the right ear was assessed by pure-tone stimulation and recordings from neurons in the left IC. Neural audiograms for each animal showed a residual deficit in most cases. Following 24-60 hr survival, the animals were perfused and the right ear was examined. Brain-stem sections were reacted with tetramethylbenzidine. Outer and/or middle ear pathology was present in over half of the animals. However, the cochleas appeared to be normal and the spiral ganglion cells were normal by several quantitative criteria: number, area, and nucleolar eccentricity. The volume of each division of the cochlear nuclei (CN) and the areas of individual neurons in the anteroventral CN were the same on the right and left sides. The number of CN neurons retrogradely labeled from the left IC injection of WGA-HRP was found to be significantly increased in the left CN, relative to normal animals, when expressed as a ratio of the number labeled in the right CN. We conclude that the residual hearing loss in the previously plugged ears was predominantly or exclusively conductive. Neonatal, unilateral conductive hearing loss in the ferret does not lead to degeneration of the CN on the side of the loss, but it does lead to at least one rearrangement of auditory brain-stem connectivity. We suggest that the extent to which the brain stem is modified by early auditory deprivation is dependent on the type, degree, and symmetry of the hearing loss.

https://www.jneurosci.org/content/jneuro/9/4/1213.full.pdf

Auditory brain stem of the ferret: some effects of rearing with a unilateral ear plug on the cochlea, cochlear nucleus, and projections to the inferior colliculus

It has been hypothesized that the dendritic field size of individual retinal ganglion cells is regulated early in development by interactions among neighboring cells (Wassle and Reiman, Proc. R. Soc. Lond. B. 200:441-461, 1978). An opportunity to test this hypothesis is provided by the consequences of prenatal enucleation that results in an increased density of ganglion cells in the remaining retina (Chalupa et al., Neuroscience 12:1139-1146, 1984). In the present study we compared dendritic field diameters of alpha ganglion cells in normal retinas to those of adult cats that were monocularly enucleated before birth (on embryonic days 42 and 51) and 6 days after birth. In each animal ganglion cells were labeled by central injections of horseradish peroxidase. The retinas were incubated according to a modified Hanker-Yates procedure and whole-mounted. All cells were sampled from the temporal retina along a corridor established by a line drawn through the optic disk and the area centralis. Alpha cells were differentiated into ON and OFF subtypes on the basis of their level of stratification in the inner plexiform layer (Peichl and Wassle, Proc. R. Soc. Lond. B. 212:139-156, 1981). Dendritic field and soma diameters were determined from complete cell drawings by calculating the mean of the two longest orthogonal diameters. Our main findings are: Early monocular enucleation does not disrupt the mosaics of ON and OFF alpha ganglion cells in the remaining retina of adult animals. Within the retinal corridor sampled, the density of alpha cells was substantially greater than normal in the remaining retina of the prenatal enucleates at all eccentricities except the far periphery. Except at the far periphery, the dendritic field diameters of the prenatally enucleated animals were significantly smaller than normal when compared at equivalent eccentricities. However, when compared at equivalent cell densities, dendritic field dimensions in the prenatally enucleated and normal animals were found to be similar. In the prenatal enucleates the somas of these neurons were also significantly smaller than normal. If the monocular enucleation was postnatal, however, the density and the dendritic field diameters of alpha cells did not differ appreciably from normal. These results indicate that the morphology of retinal ganglion cells can be influenced by increasing the density of developing ganglion cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Retinal crowding alters the morphology of alpha ganglion cells

The functional consequences of interrupting in utero binocular interactions were studied by recording from single cells in area 17 of adult cats that had one eye removed at least 2 wk before birth. In these animals all cortical neurons could be driven by the remaining eye, and in tangential microelectrode penetrations, sequences of neurons containing a full 180-degree cycle of preferred orientations were encountered. Other response properties of cortical neurons in the prenatally enucleated animals were also normal with the notable exception that the dimensions of receptive fields were significantly smaller when compared with those of control animals. Our results indicate that orientation columns in the visual cortex can develop independently of ocular dominance columns, and they suggest that interruption of binocular interactions during prenatal development of the visual pathways may enhance the resolving power of the remaining eye.

L M Chalupa

Papers

Functional organization of the cat's visual cortex after prenatal interruption of binocular interactions