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THE ISSUE It is widely believed that one’s abilities reflect both “natural” or “inborn” influences, typically attributed to genetic or inherited potential, and their interactions with experience, from prenatal origins to continuing learning in adulthood. This implies an important role of what is often referred to collectively as “the environment.” On the other hand, children are often described as “resilient,” and both fictional and factual accounts stress the achievement of individuals in overcoming early deprivation or hardships and succeeding in adult professional worlds. An important issue is how genetics and environment interact, or how does the individual become a reflection of both her genotype and her experience? WHAT SCIENCE TELLS US Genes are the parts of DNA in the cell that carry the codes for the structure of proteins. Every cell in the body of an individual, other than reproductive cells, has the same set of genes. In humans there are estimated to be somewhat less than 40,000 of such genes; other animals may have more or fewer. Genes are regulated in their expression, such that any particular gene may be active or inactive in a cell. If a gene is active, it is expressed in a cell in the form of a protein. Proteins carry out the basic functions of the cell. Thus the nerve cells, or “neurons,” of the brain have particular genes activated whose proteins, for example, comprise the structure of the synapses through which neurons communicate or synthesize the chemical neurotransmitters used in the communication process. What makes one type of cell of the body different from another type is the pattern of gene expression of each cell and hence the proteins found in each. In contrast to the neuron, for example, a cell in a muscle would express genes involved in muscle contraction, while a cell lining the inner wall of the stomach would express proteins involved in the digestion of food. Differences between humans and other animals and between animals arise to a large extent from differences in their genes. In some cases, genes encoding the same protein in different animals may differ in details of the structure of the protein that they specify; in other cases, genes may be truly unique, such as that encoding the structure of the venom in certain poisonous snakes. Differences between individual humans can also arise from differences in the structure of individual genes or from the presence or absence of genes. Many disabling conditions result from the loss or functional impairment of a single gene, and the presence of different forms of a gene can determine the likelihood of developing conditions such as Alzheimer’s disorder later in life. {examples? FXS?} Likewise, desirable characteristics can be encoded in particular genes. Many centuries before humans knew about genes they knew about inheritance of characteristics and selectively bred domesticated animals such as horses, cattle and dogs that exhibited characteristics most appropriate to their designated roles; some breeds of horses were swift and agile while others emphasized the strength necessary to carry or pull large loads. Dogs could be bred to herd sheep or cattle or to hunt edible wild birds. So how do genes give rise to such characteristics? These arise from what the proteins encoded in the genes do at the level of the body’s cells. Most processes that occur in cells involve multiple proteins and hence the activity of multiple genes. The creation of a new synapse in development involves at least several dozen, and possibly hundreds, of genes. Genes are often involved in more than one cellular process. Genes involved in muscle contraction also form parts of the synapses that activate the muscle, and of synapses in other types of cells. In most cases we are still early in the process of learning the roles of particular proteins in various cellular processes. We cannot, for example, specify the majority of the proteins that are involved in making either new synapses or new memories in the brain. Genes don’t specify protein structure directly but act through an intermediary, “messenger RNA” (mRNA), which carries the genetic message regarding protein structure to specific locations in the cell where the protein is to be synthesized. Thus some proteins involved in the structure of the synapse can be made locally at the synapse, while those involved in producing metabolic energy can be made where extra energy is needed. A gene that is active in the cell is one that is producing mRNA. In any given cell, while thousands of genes may be active, thousands of others are inactive. Genes whose proteins are involved in the general processes of energy production are active in most of the body’s cells most of the time. Genes can be activated by cellular needs; some of the proteins necessary to digest chemically different sugars are produced via gene activation only when particular sugars are present. So how do genes and experience interact? This question is still being answered, but we do know that synthesis of some proteins can be activated by behavioral experience. For example, the fragile X mental retardation protein, the absence of which causes debilitating mental retardation, is synthesized in response to behavioral experience. Likewise, the protein CREB, which activates genes thought to be involved in memory, is itself activated by behavioral experience. Other genes termed “immediate early genes” are activated by behavioral experience and in turn activate genes that may allow neurons to store information arising from the experience. A simple model for how experience interacts with genes to determine the characteristics of the child or developing animal is that the experience activates mechanisms in some cells that in turn activate genes either directly or by altering the synthesis of the proteins that they encode. Some proteins serve in “signaling pathways” that specify many kinds of changes within cells. Experience is encoded in neural activity (“action potentials,” or “nerve impulses”) which is conducted from the sensory receptors—e.g., in the retina of the eye—to brain structures that, for example, process the visual information. When the neural activity reaches synapses in the brain, in addition to triggering nerve impulses in the postsynaptic neurons, it may activate signaling pathways that can switch on genes or protein synthesis that may strengthen or stabilize synapses, altering the brain’s “wiring diagram.” At the next level—that of the neuron and its connections with others—the question is how do these experience-gene-protein interactions affect neurons (and other brain cells) in ways that alter behavioral abilities or tendencies? How does experience contribute to the functional organization of the brain? This is an area in which neuroscientists have begun to generate some very interesting answers. During particular times during development, which have been referred to as “sensitive” or “critical” periods, developing animals and humans need to undergo certain experiences if development is to proceed normally. For example, experience viewing a patterned visual environment is necessary to the development of normal visual ability. A kitten, monkey or human deprived of such experience (in humans, due to extremely poor uncorrected vision, for example) will have impaired vision even after the optical deficits are corrected with eyeglasses or surgery. At a neural level, what happens is (synapse stabilization and elimination) At a cell-molecular level, what happens is (synthesis of protein; is there a CREB tie-in to early visual development?)