Developmental changes in heterogeneous patterns of neurotransmitter receptor binding in the human interpeduncular nucleus

Abstract

The interpeduncular nucleus (IPN) exhibits many complex features, including multiple subnuclei, widespread projections with the forebrain and brainstem, and neurotransmitter heterogeneity. Despite the putative importance of this nucleus, very little is known about its neurochemical development in the human. The human IPN is cytoarchitectonically simple, unlike the rat IPN, which displays considerable heterogeneity. In the following study, we hypothesized that the developing human IPN is neurochemically heterogeneous despite its cytological simplicity. The chemoarchitecture in this study was defined by neurotransmitter receptor binding patterns by using quantitative tissue autoradiography for the muscarinic, nicotinic, serotoninergic, opioid, and kainate receptors. We examined neurotransmitter receptor binding in the developing human IPN in a total of 15 cases. The midbrains of five midgestational fetuses (19-26 gestational weeks) and six infants (38-74 postconceptional weeks) were examined. The midbrain of one child (4 years) and three adults (20-68 years) were analyzed as indices of maturity. At all ages examined, high muscarinic binding was localized to the lateral subdivision of the IPN, high serotoninergic binding was localized to the dorsal IPN, and high opioid receptor binding was localized to the medial IPN. The developmental profile was unique for each radioligand. We report a heterogenous distribution of neurotransmitter receptor binding in the developing human IPN, which supports a complex role for it in human brain function.

Hypoxic-Ischemic Encephalopathy in the Term Infant

“…Autoradiographic studies in human postmortem tissue indicate that AMPA and/or kainate receptor binding is elevated in these vulnerable regions in the midgestation fetus and neonate59, 60 and then declines at later ages, while NMDA receptor binding is undetectable at midgestation and then matures in the postnatal period. Elevated levels of AMPA/kainate receptors in the griseum pontis at midgestation and early infancy may be relevant to pontosubicular necrosis from HI during the last trimester and early infancy 60.…”

Analgesia induced by local plantar injections of opiates in the formalin test in infant rats

“…There are no reasons to assume that changes in sensory thresholds are the same in neonates and adults nor is there any reason to assume that they have a similar developmental course. There are a number of developmental processes (e.g., development of receptors, perineurial barrier, and so forth) that would suggest that the peripheral analgesic and anti-inflammatory actions of opiates may differ from those of the adult animal (Bellanti et al, 1994;Kar & Quirion, 1995b;Kristensson & Olsson, 1971;O'Grady & Hall, 1992;Panigrahy, Sleeper, Assmann, Rava, White, & Kinney, 1998;Rahman, Dashwood, Fitzgerald, Aynsley-Green, & Dickenson, 1998;Toianen, Uksila, Leino, Lassila, Hirvonen, & Ruuskanen, 1981;van Rees, Dijkstra, & Sminia, 1990;Zhu, Hsu, & Pintar, 1998b). There are two implications of this immaturity.…”