Structural plasticity · Grey Matter

Structural plasticity is the physical rewiring of the brain by growing, enlarging, shrinking and removing synapses, mostly visible as the turnover of dendritic spines, and it is how learning changes which neurons are connected as well as how strongly.

Structural plasticity. Structural plasticity is the physical rewiring of the brain by growing, enlarging, shrinking and removing synapses, mostly visible as the turnover of dendritic spines, and it is how learning changes which neurons are connected as well as how strongly.

Dendrites are the branched input trees of a neuron, and in pyramidal cells most excitatory synapses sit on dendritic spines, small protrusions under a micrometre long, each with a head that carries one synapse and a thin neck. Spine density reaches several per micrometre of dendrite, so a large cortical pyramidal cell carries thousands to tens of thousands of them, more in humans than in mice because human cells are larger. The neck isolates the head chemically: calcium entering through NMDA receptors stays largely in its own spine, which lets each synapse change on its own.

Spines come and go, less in adults. Two-photon imaging of the mouse cortex shows that in adult animals about three quarters of spines persist for weeks or longer, while a minority appear and disappear within days; in young animals turnover is much higher.

Size tracks strength. Long-term potentiation enlarges the spine head along with its AMPA receptors, and large mushroom-shaped spines are the most stable; LTD shrinks spines and can lead to their loss.

Learning leaves marks. Motor or sensory training in mice adds new spines on specific dendrites, some of which survive for months and correlate with retention of the skill; microglia help remove the ones that are pruned.

A spine is a synapse with its own small room.

Separating each input in its own compartment lets the brain strengthen, weaken, add or remove connections one at a time.

Questions: How many synapses does a brain have, and how many does one neuron receive? Estimates for the adult human brain range from about 100 to 500 trillion synapses, with about 150 trillion in the neocortex alone, roughly a billion in every cubic millimetre of cortex. A cortical or hippocampal pyramidal cell receives thousands to tens of thousands of synapses, most of its excitatory ones on dendritic spines, and the number varies widely by cell type and region. These counts mean that each neuron hears from thousands of others at once, and that the brain's storage lies in the pattern of strengths across these synapses more than in the neurons themselves. How do microglia decide which synapses to remove? During development, weak or little-used synapses become coated with complement proteins (C1q, then C3), the same tags the immune system uses to mark bacteria for destruction. Microglia carry the matching receptor, CR3, and engulf the tagged terminals; in the developing visual thalamus of mice, fragments of retinal terminals end up inside microglial lysosomes, and inputs that are less active are removed preferentially. Mice lacking C3 or CR3 keep too many synapses. Signals on healthy synapses that hold microglia back, such as CD47, protect the connections the circuit uses. How stable are dendritic spines in the adult cortex, and does learning make new ones? Imaging the same dendrites over weeks in the mouse neocortex shows that in six-month-old mice about three quarters of spines persist for at least eight days, and spines that survive that long almost all last the rest of the observation; a minority are transient, appearing and vanishing within a few days. Turnover is much higher in young animals and falls with age. Learning a new motor or sensory task adds new spines on particular dendrites, some of which stabilise along with the skill, while potentiated spines enlarge. The adult cortex is therefore mostly stable, with a small turnover that learning can bias. What does prolonged high cortisol do to neurons? Brief rises in cortisol help the brain store important events, but long exposure works differently. In animal studies, weeks of high glucocorticoid levels or chronic stress shorten and simplify the dendrites of hippocampal and prefrontal pyramidal cells and reduce their spines, while dendrites in the amygdala grow. These changes impair learning that depends on the hippocampus and flexible control by the prefrontal cortex, and in animals they largely reverse after the stress ends. Because the hippocampus also helps switch the stress axis off, damage to it can weaken that brake and prolong the exposure.