Synaptic pruning
Synaptic pruning, a phase in the development of the nervous system, is the process of synapse elimination that occurs between early childhood and the onset of puberty in many mammals, including humans.
Synaptic pruning was traditionally considered to be complete by the time of sexual maturation, but MRI studies have discounted this idea.
[5][need quotation to verify] At birth, the neurons in the visual and motor cortices have connections to the superior colliculus, spinal cord, and pons.
[7] Despite the fact it has several connotations with regulation of cognitive childhood development, pruning is thought to be a process of removing neurons which may have become damaged or degraded in order to further improve the "networking" capacity of a particular area of the brain.
In a study conducted in 2007 by Oxford University, researchers compared 8 newborn human brains with those of 8 adults using estimates based upon size and evidence gathered from stereological fractionation.
They showed that, on average, estimates of adult neuron populations were 41% lower than those of the newborns in the region they measured, the mediodorsal thalamic nucleus.
[8] The structure of the brain is thought to change when degeneration and deafferentation occur in postnatal situations, although these phenomena have not been observed in some studies.
[9][10] One theory of why many brains are synaptically pruned when a human or other primate grows up is that maintenance of synapses consume nutrients which may be needed elsewhere in the body during growth and sexual maturation.
The empirical observation that human brains fall into two distinct categories, one that reduces synaptic density by about 41% while growing up and another synaptically neotenic type in which there is very little to no reduction of synaptic density, but no continuum between them,[citation needed] is explainable by this theory as an adaptation to physiologies with different nutritional needs in which one type needs to free up nutrients to get through puberty while the other can mature sexually by other redirections of nutrients that do not involve reducing the brain's consumption of nutrients.
In small-scale axon arbor pruning, neural activity is thought to be an important regulator,[citation needed] but the molecular mechanism remains unclear.
Denervation studies at the neuromuscular junction of vertebrates have shown that the axon removal mechanism closely resembles Wallerian degeneration.
Guidance molecules serve to control axon pathfinding through repulsion, and also initiate pruning of exuberant synaptic connections.
Semaphorin ligands and the receptors neuropilins and plexins are used to induce retraction of the axons to initiate hippocampo-septal and infrapyramidal bundle (IPB) pruning.
This suggests that pruning is triggered once the ligand reaches threshold protein levels within a few days after detectable mRNA expression.
Forward signaling between ephrin-A and EphA, along the anterior-posterior axis, has been found to inhibit retinal axon branch formation posterior to a terminal zone.
[15] Reverse signaling between ephrin-B proteins and their Eph receptor tyrosine kinases have been found to initiate the retraction mechanism in the IPB.
Ephrin-B3 is observed to transduce tyrosine phosphorylation-dependent reverse signals into hippocampal axons that trigger pruning of excessive IPB fibers.
The binding of Dock180 increases Rac-GTP levels, and PAK mediates the downstream signaling of active Rac that leads to the retraction of the axon and eventual pruning.
Microglia-mediated synaptic pruning has also been observed to be upregulated during late adolescence and early adulthood, which could also account for the age of onset for schizophrenia often being reported around this time in development (late teens to early 20s for men, and mid-to-late 20s for women) [20] The drug minocycline, a semisynthetic brain-penetrant tetracycline antibiotic, has been found to somewhat reverse these changes made to patient synaptosomes by downregulating synaptic pruning.
