Afferent regulation of neurons in the brain stem auditory system

We have reviewed a series of experiments which begin to examine the cellular events underlying afferent regulation of neuronal structure. Our initial interest in such experiments stemmed from a desire to understand the cellular nature of experiential influences on brain development. While this remains a long-range goal, it's elusive nature has become increasingly apparent; how will we know when such a goal is achieved? On the other hand, it has become increasingly clear that by approaching this question as a subset of the larger problem of tissue interactions regulating nervous system structure and function, some progress is possible. In this respect, understanding afferent regulation is part and parcel of understanding "competition." Both exemplify the fact that we are dealing with a dynamic system, where changes in the balance of extracellular factors result in a cascade of events defining a new "steady state." Unfortunately, most of our methods are limited to taking "snap-shots" of a few parameters and attempting to reconstruct an epic. Our analyses of the postsynaptic events following cochlea removal have only scratched the surface. They are beginning to reveal myriad cellular processes that are dramatically altered by changing the balance of synaptic activity, or "synaptic drive," in a neuronal system. We have been continually struck by the rapidity of these postsynaptic changes when the manipulations are performed on immature animals. While the kinetics of metabolic and structural events we have studied do not yet match those of ionic events involved in information transmission, the two classes of intercellular communication are coming much closer. Some neuromodulators can alter synaptic currents for up to many seconds, and we have shown that altering afferent activity can cause changes in protein synthesis within a few minutes. The merging of these two classes of phenomena should come as no surprise since our studies and many others have definitively linked a variety of metabolic and structural events to changes in the synaptic drive between two neurons. On the other hand, this progress does highlight the need for increased attention to the short-term changes following manipulations of afferent activity. Hopefully such studies will lead to an understanding of the intracellular chain of events responsible for the regulation of neuronal form. A second area of interest has been the age restrictions on the events we have studied.(ABSTRACT TRUNCATED AT 400 WORDS)