Neuronal differentiation factors/cytokines and synaptic plasticity

As in the hematopoietic system, the enormous variety of phenotypes in the nervous system arises, in part, through the action of instructive differentiation signals. Such signals include secreted and cell-bound proteins as well as steroid hormones. Since these agents have broad effects on cell proliferation and gene expression in many different tissues, the term cytokines is being adopted for the proteins. The original meaning of that term refers to cell movement, an activity that the present proteins could turn out to share (Cohen et al., 1974; see also Nathan and Sporn, 1991). Our focus here is on the regulation of neuronal gene expression by these factors, particularly the genes that code for neuropeptides and the enzymes that synthesize neurotransmitters, because these are the molecules directly responsible for transmission of information at synapses. We highlight parallels between the control of phenotypic expression in the nervous and hematopoietic systems and between the cytokines involved in the immune response and the response of the nervous system to injury. Attention is also drawn to a potential role for cytokines in synaptic plasticity. For instance, changes in transmission at particular synapses that underlie distinctive behavioral states are often associated with alterations in the expression of the neurotransmitters and neuropeptides employed at those synapses. Such changes in expression can also occur during daily or monthly physiological changes in the body. Moreover, certain paradigms widely used to study the phenomena of learning and memory have, in a few cases, suggested an involvement of cytokines in the plasticity of synaptic transmission.