that social isolation of mice leads to reduced myelin thickness and poor working memory, but only during a juvenile critical period. In primates, isolation is correlated with abnormal changes in white matter potentially due to decreased myelination. In all, myelin and its associated receptors bind several important axonal growth inhibitors which help close the critical period. The timing of this myelination, however, is dependent on the brain region and external factors such as the social environment. Neuromodulation While the presence or absence of sensory experiences most robustly shapes brain development during the critical period, the behavioral context (i.e. the amount of attention, arousal, fear and reward experienced) concurrent with the sensory inputs have been suggested to be important in regulating the brain remodeling mechanisms. In terms of brain connectivity, these behavioral and contextual inputs activate the neuromodulatory system, which have substantial connectivity to the cortex The molecular effectors released by the neuromodulatory system are called neuromodulators, which include acetylcholine, dopamine, and noradrenaline among others. Investigating the effect of these molecules, as well as the neurons that release and bind them, has been one approach to elucidate the biology of neuromodulation. Research using this approach has highlighted the role of neuromodulation in sensory processing during the critical period. For example, on the one hand, in kittens, a shift in ocular dominance resulting from monocular deprivation during the critical period is reduced by combined destruction of noradrenergic and cholinergic neurons. In addition, prenatal exposure to selective serotonin reuptake inhibitors (SSRI) causes a shift in perceptual narrowing on language to earlier in development. On the other hand, neuromodulatory stimulation has been shown to induce brain plasticity in adult mice. While being subjected to cholinergic or dopaminergic stimulation, adult mice listening to a tone of specific frequency exhibited expansion of the tonotopic area in the auditory cortex that responds specifically to sounds of that frequency. Mechanistically, neuromodulation is increasingly being recognized for its fine-tuning of the PV cell-mediated inhibition of excitatory pyramidal neurons' soma. Central to the neuromodulatory regulation of PV cell activity is the existence of distinct subsets of inhibitory neurons, which are responsive to activation by neuromodulators and which inhibit PV cells. Within these cells, some also inhibit specific pyramidal cell dendrites. By inhibiting PV cells activity, the neuromodulator-sensitive inhibitory cells such as those expressing Vasoactive intestinal peptide (VIP) or somatostatin (SST) lift the inhibition of the pyramidal neurons; in other words,