Neurogenesis and NeuroDevelopment, The Birth of Neurons

Neurogenesis and NeuroDevelopment

- The Birth of Neurons

Neurogenesis or Neuro Genesis is the process of birth of neurons.

The neurogenesis in the human adult brain was discovered the early 1980s, surprising the scientific community and the traditional neuroscientists, who thinked were born with all the neurons we were ever going to have.

Scientists believed that once a neural circuit was in place, adding any new neurons would disrupt the flow of information and disable the brain’s communication system.
Neuroscientists reviewed their discover and saw that it worked in several animals and to the human adult brain as well.

As children we might produce some new neurons to help build the pathways - Called neural circuits -that act as information highways between different areas of the brain.

Humans and Dolphins: Decline and Fall of Adult Neurogenesis. National Institutes of Health (.gov) - Analyses carried out in dolphins, mammals devoid of olfaction, but descendant of ancestors provided with olfaction, has shown disappearance. Topics: adult neurogenesis, brain plasticity and aging, comparative anatomy, doublecortin and immature neurons.
Pre-clinical research is carried out on animal models, mostly laboratory rodents, with the ultimate aim of translating the acquired knowledge to humans. In the last decades, adult neurogenesis (AN) has been intensively studied since it is viewed as a tool for fostering brain plasticity, possibly repair. Yet, occurrence, location, and rate of AN vary among mammals: the capability for constitutive neuronal production is substantially reduced when comparing small-brained, short living (laboratory rodents) and large-brained, long-living species (humans, dolphins). Several difficulties concerning scarce availability of fresh tissues, technical limits and ethical concerns did contribute in delaying and diverting the achievement of the picture of neurogenic plasticity in large-brained mammals. Some reports appeared in the last few years, starting to shed more light on this issue. Despite technical limits, data from recent studies mostly converge to indicate that neurogenesis is vestigial, or possibly absent, in regions of the adult human brain where in rodents neuronal addition continues into adult life. Analyses carried out in dolphins, mammals devoid of olfaction, but descendant of ancestors provided with olfaction, has shown disappearance of neurogenesis in both neonatal and adult individuals. Heterogeneity in mammalian structural plasticity remains largely underestimated by scientists focusing their research in rodents. Comparative studies are the key to understand the function of AN and the possible translational significance of neuronal replacement in humans. Here, we summarize comparative studies on AN and discuss the evolutionary implications of variations on the recruitment of new neurons in different regions and different species.

Neurogenesis History

In 1962, the scientist Joseph Altman saw evidence of neurogenesis in a region of the adult rat brain called the hippocampus.
He reported that newborn neurons migrated from their birthplace in the hippocampus to other parts of the brain.

In 1979, the scientist Michael Kaplan, confirmed Altman’s findings in the rat brain

In 1983, Kaplan also found neural precursor cells in the forebrain of an adult monkey.

In 1980, the scientist Fernando Nottebohm was trying to understand how birds learn to sing noted that the numbers of neurons in the forebrains of male canaries dramatically increased during the mating season, exactly at same time in which the birds had to learn new songs to attract females.

Why did these bird brains add neurons at such a critical time in learning? Nottebohm believed it was because fresh neurons helped store new song patterns within the neural circuits of the forebrain, the area of the brain that controls complex behaviors. These new neurons made learning possible. If birds made new neurons to help them remember and learn, Nottebohm thought the brains of mammals might too. But most scientists believed these findings could not apply to mammals.

Elizabeth Gould later found evidence of newborn neurons in another area of the brain in monkeys

Fred Gage and Peter Eriksson showed that the adult human brain produced new neurons in a similar area.

For classical neuroscientists, neurogenesis in the adult brain is still an unproven theory.
But others think the evidence offers intriguing possibilities about the role of adult-generated neurons in learning and memory.

Neurulation - First stage is the Neurulation. Embryogenesis and the animal development stages. Neurulation follows gastrulation in all vertebrates. During gastrulation cells migrate to the interior of embryo, forming three germ layers (endoderm, mesoderm and ectoderm) from which all tissues and organs will arise. In a simplified way, it can be said that the ectoderm gives rise to skin and nervous system, the endoderm to the guts and the mesoderm to the rest of the organs. After gastrulation the notochord -a flexible, rod-shaped body that runs along the antero-posterior axis -has been formed (derived from mesoderm). the notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm, composed of neuronal precursor (or stem) cells. This is evidenced by a thickening of the ectoderm above the notochord, the neural plate. the neural plate will form the neural tube which then twists, turns and kinks to form the three primary brain vesicles and five secondary brain vesicles. the end result of this process is described in the article on the regions of the brain.

Steps of Development and Placement of Neurons

Proliferation

Proliferation or (cell generation by mitosis) occurs inside neural tube. Neurogenesis term used to describe the production of nerve cells.
Mitotic cycle of each cell follows a fixed sequence, resulting in production of neuroblasts (nerve cell precursors) or glioblasts (glial cell precursors).

Migration

process starts after proliferative phase (but not before 6 wks gestation), when neuroblasts move to a permanent location. The migration process is as follows:
Early neural tube consists of ventricular zone of mitotic cells and marginal zone of cellular processes
Intermediate zone forms with cell proliferation
By 8-10 weeks after conception, intermediate zone enlarges to form cortical plate
Initial formation of cortical plate occurs by migration of cells to sixth layer of cortex and subsequent migrations follow an inside-out pattern (thus, top layer is formed last by neurons that must migrate past cells of the deeper layers)
Second migratory wave is at 11-15 weeks gestation
Cells migrate in sheets called laminae
Migration occurs by guidance by radial fibers
Radially oriented glia - group of glial cells radially oriented from ventricular to basal surface and guides migration of neurons
Migration in cerebellum occurs in outside-in pattern- b/w 9-13 wks gestation, neuroblasts migrate to outermost layer of cerebellum and proliferate. Bergmann glia responsible for migration
By 18 weeks gestation, all cortical neurons have reached designated location
Migratory defects include complete failure of migration; curtailment of migratory cells along migratory pathway; aberrant placement of postmitotic neurons within target structure (ectopia)

Aggregation

- during migratory cycles, neurons selectively aggregate to form cellular masses, or layers. This is called lamination. Two events in aggregation process
neurons come together and establish adhesion between necessary cells
align themselves with respect to immediate neighbors

Cytodifferentiation

Cytodifferentiation or cellular differentiation. Four major concurrent aspects. Development of cell body.
Selective cell death: 40-75% of all neurons die during development; only a limited number of neurons succeed in sending axons to correct targets

Dendrites

Axonal and dendritic development process. Dendritic growth begins prenatally and proceeds slowly.
As migrating neuronal cells reach designated position, the dendrites begin to sprout (arborization), and extensions (spines) begin to extend.
Majority of arborization and spine growth occurs postnatally, with most intensive period occurring birth to 18 months. Development highly sensitive to environmental stimulation.
BioChemystry : biochemical specificity programmed into each nerve cell determining that contacts between cells are made. As neuron forms axon and dendrites, sends out advance spray of cellular processes (microfilaments) that seek chemical attraction, forming appropriate connections with nerve cells.

Synaptogenesis

The termination of axonal growth, selection of synaptic sites, and formation of synapse; regional increases in synaptic density accompany the emergence of function:
Visual cortex : dendritic and synaptic growth stops at age 8 months, but process of synapse elimination continues to 3 years of age
Frontal cortex : dendritic and synaptic density reach peak in infancy and early childhood and decline b/w 2 and 16 yrs

Pruning

The neurons overproduced and many initial connections are random; subsequent development eliminates (prunes) neurons.
Process often begins at dendritic spines.
Purposeful sculpting of brain; eliminates weakly reinforced or redundant connections.
Promotes neural efficiency.
Primarily a postnatal process, eliminating 40% of cortical neurons during childhood.
Proceeds at different times and rates. Ex- pruning of visual cortex begins at 1 and complete by 12 yrs; pruning of prefrontal from 5-16 yrs.