EXPRESSION OF ALPHA-7 NEURONAL NICOTINIC RECEPTORS DURING POSTNATAL-DEVELOPMENT OF THE RAT CEREBELLUM

Several lines of evidence suggest that alpha-bungarotoxin-sensitive ne uronal 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 th e brain, including the cerebellum, where it is present almost exclusiv ely in Purkinje cells and deep cerebellar nuclei. Purkinje cells const itute the only efferent pathway of the cerebellum and their developmen t involves complex interactions, which have been extensively studied. They therefore provide a potentially useful model for analysis of deve lopmental plasticity which could be influenced by alpha 7 neuronal nic otinic receptors, In the present study a previously characterized mono clonal antibody (mAb 307) has been used to determine the temporal patt ern of expression of the alpha 7 subunit in the developing rat cerebel lum. No detectable alpha 7 immunoreactivity is found between P0 and P2 . Between P3 and P5, however, the Purkinje cell layer shows moderate i mmunolabeling. alpha 7 expression in this layer increases rapidly betw een P8 and P15. This increase in alpha 7 staining, which overlaps in t ime with important developmental and synaptogenic events, is not unifo rm throughout the cerebellar cortex. Thus, between P3 and P5 all Purki nje cells are weakly labeled, while at later stages (P8-P15) immunolab eling becomes more intense but, at the same time, disappears from Purk inje cells in rostral lobules, In addition, a very well defined patter n of discontinuous or columnar labeling is detected in regions of the Purkinje cell layer where alpha 7 subunits are being expressed. Finall y, at P20, alpha 7 subunit labeling is found again in all Purkinje cel ls, although with lower intensity. These results suggest that alpha 7 receptor expression is developmentally regulated, with a time course t hat parallels the final differentiation of Purkinje cells. In addition , the heterogeneous spatial distribution of alpha 7-containing nicotin ic receptors indicates that, during cerebellar maturation, these cells may receive different signals that modulate receptor gene expression in a very specific way.