(USMLE topics, neurobiology) What is Synaptic Pruning? Impaired pruning and link to neurological disorders.
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Synaptic pruning is the process of synapse removal that takes place naturally, as part of brain maturation. A human brain starts its development in early embryonic stage and reaches the maximum number of synaptic connections sometime in early childhood, at which point it is about double of what is normally present in an adult brain. This is when the elimination of excess neuronal synapses, known as synaptic pruning, begins. The process removes roughly half of all synapses, and occurs mainly during adolescence, but may continue well into young adulthood. By getting rid of unnecessary connections, synaptic pruning helps to refine neural circuits and increase network efficiency.
Computational models suggest that learning performance is optimal when synaptic connections are first over-generated and then pruned. An analogy is the task of writing an essay: the easiest way is to put all possible ideas into a longer-than-needed first draft, then trim it to keep only the essential points to create an effective final message.
Synaptic pruning is activity-driven, and follows the “use it or lose it” rule - synapses that are rarely used are eliminated, while frequently used synapses are protected from removal. In fact, it has been shown that activation of the glutamate receptor NMDA, a marker associated with long-term memory retention and learning, is the major protective factor for a synapse. Thus, active synapses are selectively stabilized, while superfluous synapses are eliminated.
While the mechanism underlying synaptic pruning is, in most part, still a mystery, recent studies have implicated the brain’s supportive cells, known as glial cells, or glia. Specifically, two types of glia - astrocytes and microglia - are responsible for identifying and removing unnecessary neural connections. A number of signaling molecules are involved in control of glial cell movement, target recognition and ingestion.
Given the important role of synaptic pruning in sculpturing and refining the brain’s neural circuits, it is plausible that aberrant synaptic pruning is associated with a number of neurological disorders such as schizophrenia, autism and epilepsy. Too much pruning results in shortage of connections and is thought to underlie schizophrenia. The first occurrence of schizophrenia symptoms, typically in late adolescence or early adulthood, coincides with the time when synaptic pruning is most prominent.
Too little pruning, on the other hand, leaves the brain with too many redundant connections, which can be confusing, inefficient and may limit learning potential. Excessive synapses are observed in autism spectrum disorders, and epilepsy.