Acetylcholinesterase in immature thalamic neurons: Relation to afferentation, development, regulation and cellular distribution

Abstract

The transient appearance of intense acetylcholinesterase reactivity in some immature, noncholinergic neurons has not been adequately explained. In this study two questions were investigated that relate to several possible roles for acetylcholinesterase. First, what factors influence the onset and maintenance of reactivity? Second, what are the temporal and spatial features of the cellular expression in relation to stages of neuronal development? Using light- and electron-microscopic histochemical methods, the non-cholinergic ventrobasal complex in thalamus of the immature rat was examined. Ultrastructural observations on fetal ventrobasal complex demonstrated that the onset of acetylcholinesterase reactivity precedes ingrowth of most extrinsic afferents. These inputs are, therefore, unlikely to provide the signal for onset. In transplants and expiants, acetylcholinesterase persisted in ventrobasal complex neurons independent of their principal afferents. However, afferentation can affect reactivity. The patterned variation in intensity, characteristic of infant ventrobasal complex, was dramatically altered by unilateral interruption of its afferentation. The changes in intensity patterning could reflect changes in acetylcholinesterase metabolism, since postnatal treatment with an irreversible inhibitor (diisofluorophosphate) in vivo demonstrated resynthesis of acetylcholinesterase. The period of peak intensity of acetylcholinesterase reactivity normally began abruptly at 18 days of gestation ±12 h and continued until 4–6 days postnatally. This period follows neurogenesis and migration, but precedes active synaptogenesis. It coincides with outgrowth and initial contacting of cell processes in the ventrobasal complex. The timing complements the ultrastructural finding that acetylcholinesterase-dependent reaction product most commonly is localized to small patches of surface membrane, where distal processes contact each other, non-synaptically. Together these data suggest three points. First, that the expression of acetylcholinesterase in the immature ventrobasal complex neuron is probably under active metabolic control, responsive to both intrinsic and environmental factors. Second, that acetylcholinesterase expression is unlikely to result from a transient cholinergic input. Third, that the temporal and spatial characteristics of histochemical reactivity enable exclusion of several previously suggested explanations for the occurrence of acetylcholinesterase in the ventrobasal complex. At the same time, these data provide a basis for a first-order hypothesis: acetylcholinesterase plays a role in the formation of early intercellular relationships and/or process outgrowth. Possible mechanisms for these roles are discussed that would be consistent with the present data.