PRESYNAPTIC AND POSTSYNAPTIC SUBCELLULAR-LOCALIZATION OF SUBSTANCE-P RECEPTOR IMMUNOREACTIVITY IN THE NEOSTRIATUM OF THE RAT AND RHESUS-MONKEY (MACACA-MULATTA)

The substance P receptor (SPR)gene is expressed at high levels in basa l ganglia, but the paucity of information about localization of the en coded receptor protein has limited our understanding of this peptide's involvement in cellular and subcellular mechanisms in this region. Mo rphological evidence in the rodent striatum indicates that SPRs are ex pressed in postsynaptic neuronal elements, while pharmacological studi es suggest the existence of presynaptic SPRs in this structure. We hav e examined the issue of subcellular distribution of this receptor prot ein in rat and primate neostriatal tissue, employing an antiserum rais ed against SPR. Electron microscopic analysis revealed that SPR immuno reactivity is present in presynaptic and postsynaptic neuronal element s in both species. In agreement with earlier studies, SPR immunoreacti vity was found predominantly in perikarya and dendrites of a small sub set of striatal neurons, the large and medium-sized aspiny interneuron s. In addition, a small but significant proportion of the immunoreacti on product was localized in presynaptic profiles, both in axons and ax on terminals. The majority of SPR immunoreactive boutons formed asymme tric synapses with dendrites and dendritic spines. The association of SPRs with asymmetric synapses provides a morphological substrate for p eptidergic modulation of excitatory neurotransmission of extrastriatal origin. A minor proportion of immunolabeled axons established symmetr ic synaptic junctions with unlabeled dendrites. The presence of SPRs i n these synapses suggests a presynaptic peptidergic modulation of intr insic striatal transmitter systems. The observations in this study als o indicate that SPR mediates a complex combination of postsynaptic and presynaptic effects on acetylcholine release in the mammalian striatu m. (C) 1996 Wiley-Liss, Inc.