Effects of increased neural activity on brain growth.

Abstract

We have measured the effects of regionally increased metabolic activity-and by inference electrical activity-on cortical growth in the developing rat brain. Cortical growth is significantly and specifically greater in regions of chronically increased activity. This effect of activity on cortical growth may help explain the permanent storage of early experience in the developing nervous system.The mammalian brain grows progressively in postnatal life, increasing in weight about 4-fold from birth to maturity in man and mouse (1-3). In the work reported here we have tested the hypothesis that this gradual enlargement is modulated by experience, regional growth being increased by locally augmented neural activity (4-6).Using the somatosensory cortex of the rat, we have taken advantage of previous studies that showed that the growth of one sensory system in the rodent brain can be enhanced by depriving the animal of a different sensory modality (7-9). Thus, neonatal eye removal in mice causes an enlargement of the cortical barrels (and neurons) that represent the mystacial vibrissae. These studies did not, however, examine levels of neural activity in the affected cortex or relate neural activity to cortical growth. Accordingly, we have asked whether metabolic activity, measured by the index of blood vessel density (4, 10, 11), is increased in the somatic sensory cortex of the enucleated animals and if changes in activity are associated with regionally specific enhancement of cortical growth during development. Since most of the energy demand on neurons is generated by synaptic signaling, local levels of metabolism reflect regional differences in the brain's electrical activity (12-15).Our results show that bilateral eye removal at birth increased capillary density in the primary somatic sensory cortex (S1) and its component parts. Moreover, each of the cortical areas with chronically augmented levels of metabolic activity grew larger than its counterpart in control animals, whereas adjacent cortical areas with normal levels of activity did not. MATERIALS AND METHODSSix litters of male Long Evans (pigmented) rats from Charles River Laboratories were used in these experiments. Half of the pups in each litter underwent bilateral enucleation within 24 hr of birth; the other half served as controls. After inducing surgical anesthesia by cooling (16), both globes were removed. The remaining (control) animals in the litter were anesthetized only. Each litter was kept together until weaning; subsequently, experimental and control animals were fostered three or four per cage until 10-12 weeks of age. The animals were then anesthetized with pentobarbital (250 mg/kg) and perfused as described (4). Serial tangential sections (35 gm) were prepared for cytochrome oxidase histochemistry to demonstrate the primary somatic sensory cortex, the primary auditory cortex, the primary visual cortex, and the striatum. All slides were coded so that measurements were made without knowledge of an animal's history. Images of the ink-fi...

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