Synaptic Pruning

The developing brain makes far more connections than it needs, then removes the unused ones. How 'use it or lose it' sculpts circuits through childhood and adolescence.

It seems backwards, but brain development involves losing a great deal. Many neurons die during normal development, and after birth the brain prunes back large numbers of synapses.

Overproduce, then select

In the 1970s and 80s the neuroscientist Peter Huttenlocher counted synapses in post-mortem human brains of different ages. Synapse density rose rapidly after birth, peaked in early childhood — in the visual cortex within the first year, in the prefrontal cortex later — and then declined substantially through adolescence toward adult levels. Work in monkeys showed similar patterns. Developing brains overproduce connections and then select among them.

Use it or lose it

Which synapses survive? Broadly, active, useful connections are strengthened and stabilised, while weak, inactive ones are removed. Hubel and Wiesel's experiments showed this for vision: when one eye was covered during development, its connections in the visual cortex lost out to the active eye's. Activity-dependent competition fine-tunes circuits to match the individual's environment.

Who does the pruning

Microglia, the brain's immune cells, engulf unwanted synapses. Proteins of the complement system, part of the immune system, tag weak synapses for removal. Astrocytes also participate.

Too much or too little?

Because pruning shapes circuits, researchers have asked whether it goes wrong in some conditions. A 2016 study found that variants of the complement gene C4 that increase its activity are associated with greater risk of schizophrenia, which often emerges in late adolescence — when cortical pruning is still active — suggesting excessive pruning may play a part. Some studies have suggested reduced pruning in autism. These remain hypotheses under active investigation.

Pruning isn't a loss

Pruning is what makes a brain efficient and specialised. A newborn can distinguish speech sounds from every language; by about a year, infants become specialists in the sounds of the language around them.