The development of enkephalin and substance P neurons in the basal ganglia: insights into neostriatal compartments and the extended amygdala.

ABSTRACT

To study the comparative development of the two major neuropeptide genes of the striatum, we used immunocytochemistry to detect immunoreactivity (ir) for substance P and synenkephalin (the N terminus of proenkephalin), and in situ hybridization to detect proenkephalin mRNA. Earliest detection of substance P-ir was in the anlage of the bed nucleus of the stria terminalis (BST, at E15) and in the rostral-lateral caudate-putamen (CPu), at E16. Substance P in the BST was immediately subjacent to the medial ganglionic eminence, while immunoreactivity in the CPu was associated with the lateral ganglionic eminence. Earliest detection of synenkephalin-ir or proenkephalin mRNA was in the caudal-lateral CPu and the adjacent central nucleus of the amygdala (Ce), at E16. Over the next several days, expression of each neuropeptide spread toward the region of first expression of the other neuropeptide. The first overlap of expression of the two neuropeptides was at E18, at the level of the septum. Despite correspondence of substance P-ir and proenkephalin mRNA in patches at P0, very little co-expression of the two neuropeptides was evident in individual neurons. We propose a model in which the CPu develops primarily from the lateral ganglionic eminence, and the extended amygdala develops primarily from the medial ganglionic eminence. Within each structure, two poles of neuropeptide gene expression are established initially substance P-ir in the rostral CPu and in the rostral-medial pole of the extended amygdala (represented by the BST), and synenkephalin/proenkephalin in the caudal CPu and in the caudal-lateral pole of the extended amygdala (represented by the Ce). A stream of substance P-ir cells connects the two poles of the extended amygdala, in the sublenticular substantia innominata.