Postnatal changes in functional activities of the pig's brain: a combined functional magnetic resonance imaging and immunohistochemical study

Developmental changes in brain activation after pain stimulation and after passive movement of the hind paw were assessed by functional magnetic resonance imaging (fMRI) in pigs of postnatal ages 2, 4 and 6 months. Response patterns were correlated with histological maturation parameters. At 2 months, fMRI failed to detect brain activation after pain stimulation and revealed weak, but widespread activation after passive movement. At 4 months, strong reaction of numerous cortical areas on the contralateral side was seen after pain stimulation. Following passive movement, activation was weaker but more widespread, and the brainstem was also involved. By 6 months, cortical activation became more restricted to the contralateral sensory cortex and brainstem after pain stimulation and to the contralateral sensory and ipsilateral premotor and motor cortices after passive movement. Neocortical synaptophysin immunoreaction increased significantly between 2 and 4 months and slightly decreased by 6 months. The density of GABA-immunoreactive neurons and fibers significantly increased, reaching a maximum at 6 months. Our studies indicate that remodeling of synapses and development of inhibitory GABA neurons last until 6 months postnatally, when the fMRI response of the pig's brain also attains its mature adult pattern.