synaptic pruning during the early visual cortex critical period. More recently, the expression of the complement component 4 gene has been found to significantly contribute to abnormally high levels of microglial synaptic pruning during early stages of development in schizophrenic neurons and microglia, suggesting a genomic connection between the immune system and critical periods. Spine motility Dendritic spine motility is the altering of the dendritic morphology of a neuron, specifically the appearing and disappearing of the small protrusions known as spines. In early postnatal development, spine motility has been found to be at very high levels. Due to its most pronounced occurrence during postnatal days 11 through 15, spine motility is thought to have a role in neurogenesis. Motility levels significantly decrease before the start of the visual cortex critical period and monocular deprivation experiments show that motility levels steadily decrease until the critical period is over, hinting that motility might not be explicitly involved in this process. However, binocular deprivation before eye-opening resulted in a significant up-regulation of spine motility until the peak of the critical period, resulting in controversial findings regarding the role of dendritic spine motility. Excitatory-inhibitory balance Another critical component of neuronal plasticity is the balance of excitatory and inhibitory inputs. Early in development, GABA, the major inhibitory neurotransmitter in the adult brain, exhibits an excitatory effect on its target neurons. However, due to changes in internal chloride levels due to the up-regulation of potassium chloride pumps, GABA then switches to inhibitory synaptic transmission. The maturation of the GABAergic inhibitory system helps to trigger the onset of critical periods. Strengthened GABAergic systems can induce an early critical period, while weaker GABAergic inputs can delay or even prevent plasticity. Inhibition also guides plasticity once the critical period has begun. For example, lateral inhibition is especially important in guiding columnar formation in the visual cortex. Hebbian theory provides insight on the importance of inhibition within neural networks: without inhibition, there would be more synchronous firing and therefore more connections, but with inhibition, fewer excitatory signals get through, allowing only the more salient connections to mature. Critical period closure Perineuronal nets Critical period closure has been shown to be modulated by the maturation of inhibitory circuits, mediated by the formation of perineuronal nets around inhibitory neurons. Perineuronal nets (PNNs) are structures in the extracellular matrix formed by chondroitin sulfate proteoglycans, hyaluronan, and link proteins. These structures envelop the soma