Synaptic pruning

Synaptic pruning, a phase in the

Pruning is influenced by environmental factors and is widely thought to represent learning.^[5]

Variations

Regulatory pruning

At birth, the neurons in the visual and motor cortices have connections to the superior colliculus, spinal cord, and pons. The neurons in each cortex are selectively pruned, leaving connections that are made with the functionally appropriate processing centers. Therefore, the neurons in the visual cortex prune the synapses with neurons in the spinal cord, and the motor cortex severs connections with the superior colliculus. This variation of pruning is known as large-scaled stereotyped axon pruning. Neurons send long axon branches to appropriate and inappropriate target areas, and the inappropriate connections are eventually pruned away.^[6]

Regressive events refine the abundance of connections, seen in neurogenesis, to create a specific and mature circuitry. Apoptosis and pruning are the two main methods of severing the undesired connections. In apoptosis, the neuron is killed and all connections associated with the neuron are also eliminated. In contrast, the neuron does not die in pruning, but requires the retraction of axons from synaptic connections that are not functionally appropriate.

It is believed that the purpose of synaptic pruning is to remove unnecessary neuronal structures from the brain; as the human brain develops, the need to understand more complex structures becomes much more pertinent, and simpler associations formed at childhood are thought to be replaced by complex structures.^[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.^[7] Furthermore, it has been stipulated that the mechanism not only works in regard to development and reparation, but also as a means of continually maintaining more efficient brain function by removing neurons by their synaptic efficiency.^[7]

Pruning in the maturing brain

The pruning that is associated with learning is known as small-scale axon terminal arbor pruning. Axons extend short axon terminal arbors toward neurons within a target area. Certain terminal arbors are pruned by competition. The selection of the pruned terminal arbors follow the "use it or lose it" principle seen in synaptic plasticity. This means synapses that are frequently used have strong connections while the rarely used synapses are eliminated. Examples seen in vertebrate include pruning of axon terminals in the neuromuscular junction in the peripheral nervous system and the pruning of climbing fiber inputs to the cerebellum in the central nervous system.^[6]

In terms of humans, synaptic pruning has been observed through the inference of differences in the estimated numbers of

All attempts to construct artificial intelligence systems that learn by pruning connections that are disused have the problem that every time they learn something new, they forget everything they learned before. Since biological brains follow the same laws of physics as artificial intelligences, as all physical objects do, these researchers argue that if biological brains learned by pruning they would face the same catastrophic forgetting issues. This is pointed out as an especially severe problem if the learning is supposed to be part of a developmental process since retention of older knowledge is necessary for developmental types of learning, and as such it is argued that synaptic pruning cannot be a mechanism of mental development. It is argued that developmental types of learning must use other mechanisms that do not rely on synaptic pruning.^[9][10]

Energy saving for reproduction and discontinuous differences

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. This theory presupposes no mental function of synaptic pruning. 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. Citing that most of the nutrient costs in the brain are in maintaining the brain cells and their synapses, rather than the firing itself, this theory explains the observation that some brains appear to continue pruning years after sexual maturation as a result of some brains having more robust synapses, allowing them to take years of neglect before the synaptic spines finally disintegrate. Another hypothesis that can explain the discontinuity is that of limited functional genetic space restricted by the fact that most of the human genome needs to lack sequence-specific functions to avoid too many deleterious mutations, predicting that evolution proceeds by a few of the mutations happening to have large effects while most mutations do not have any effects at all.^[11][12]

Mechanisms

The three models explaining synaptic pruning are axon degeneration, axon retraction, and axon shedding. In all cases, the

In Drosophila, there are extensive changes made to the nervous system during metamorphosis. Metamorphosis is triggered by ecdysone, and during this period, extensive pruning and reorganization of the neural network occurs. Therefore, it is theorized that pruning in Drosophila is triggered by the activation of ecdysone receptors. Denervation studies at the neuromuscular junction of vertebrates have shown that the axon removal mechanism closely resembles Wallerian degeneration.^[13] However, the global and simultaneous pruning seen in Drosophilia differs from the mammalian nervous system pruning, which occurs locally and over multiple stages of development.^[6]

Axon retraction

Axon branches retract in a

Microglia have been implicated in synaptic pruning, as they have roles in both the immune response as macrophages as well as in neuronal upkeep and synaptic plasticity in the CNS during fetal development, early postnatal development, and adolescence, in which they engulf unneeded or redundant synapses via phagocytosis. ^[18] Microglial synapse engulfment and uptake has been specifically observed to be upregulated in the isolated synaptosomes of male patients with schizophrenia compared to healthy controls, suggesting upregulated microglia-induced synaptic pruning in these individuals. 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.^[20]

Genes in the

• Neuroplasticity

References