The critical impact of early cellular environment on neuronal development.

Normal brain development requires the precise interactions of environmental signals with genes that drive cellular differentiation and circuit formation. Experimental studies in animal models reveal that early environmental influences in utero can modulate cell fate choice and neuronal growth. Modification of the determinants can have long-lasting consequences. Studies using transplant and cell culture methods have examined the development of the limbic system, regions of the brain that mediate cognition, emotion, memory, and learning. The results show that growth factors in the environment of progenitor cells control long-term gene expression that characterizes neurons in limbic brain regions. Other studies in which the cellular environment is altered by prenatal cocaine exposure result in modified fetal neurotransmitter function and specific pharmacological and structural alterations in the cerebral cortex that lead to abnormal behavior. The cellular milieu of the developing central nervous system prenatally thus serves functions as critical as environmental stimuli postnatally that promote synaptic development and refinement.