Expression of alpha 7 neuronal nicotinic receptors during postnatal development of the rate cerebellum.

Several lines of evidence suggest that alpha-bungarotoxin-sensitive neuronal nicotinic acetylcholine receptors may play a developmental role by modulating plasticity in neuronal circuits. The alpha 7 subunit, a main component of these receptors, is expressed in most regions of the brain, including the cerebellum, where it is present almost exclusively in Purkinje cells and deep cerebellar nuclei. Purkinje cells constitute the only efferent pathway of the cerebellum and their development involves complex interactions, which have been extensively studied. They therefore provide a potentially useful model for analysis of development plasticity which could be influenced by alpha 7 neuronal nicotinic receptors. In the present study a previously characterized monoclonal antibody (mAb 307) has been used to determine the temporal pattern of expression of the alpha 7 subunit in the developing rat cerebellum. No detectable alpha 7 immunoreactivity is found between P0 and P2. Between P3 and P5, however, the Purkinje cell layer shows moderate immunolabeling. alpha 7 expression in this layer increases rapidly between P8 and P15. This increase in alpha 7 staining, which overlaps in time with important developmental and synaptogenic events, is not uniform throughout the cerebellar cortex. Thus, between P3 and P5 all Purkinje cells are weakly labeled, while at later stages (P8-P15) immunolabeling becomes more intense, but at the same time, disappears from Purkinje cells in rostral lobules. In addition, a very well defined pattern for discontinuous or columnar labeling is detected in regions of the Purkinje cell layer where alpha 7 subunits were being expressed. Finally, at P20, alpha 7 subunit labeling is found again in all Purkinje cells, although with lower intensity. These results suggest that alpha 7 receptor expression is developmentally regulated, with a time course that parallels the final differentiation of Purkinje cells. In addition, the heterogeneous spatial distribution of alpha 7-containing nicotinic receptors indicates that, during cerebellar maturation, these cells may receive different signals that modulate receptor gene expression in a very specific way.