Description) The targeting of opioid receptors, as well as their coordinated interactions with N-methyl-D-aspartate subtype of glutamate receptors (NMDARs), is crucial for normal brain development and motor functions involving patch-matrix compartments in the mammalian caudate-putamen nucleus (CPN). During the critical developmental plasticity period, mu and delta opioid receptors (MOR, DOR) play either complementary or opposite roles that may in part involve functional interaction with NMDAR. The goal of this application is to test the hypothesis that there are age-related differences in the subcellular localization of MOR and/or DOR, which are correlated with synaptogenesis and parallel those of NMDAR in the CPN.
The specific aims i n each of the three proposed studies will be pursued by examining the localization of sequence specific antipeptide antisera against MOR, DOR, or NMDAR in the rat CPN during postnatal ontogeny. The results obtained from these studies will complement and extend previous knowledge that age-dependent MOR and DOR subcellular distributions are functionally linked to neuronal maturation; that developing NMDAR is largely involved in activity-dependent synaptic plasticity and has a subcellular distribution that parallels the distribution of opioid receptors; and that prenatal opioid availability differentially controls the ontogeny of neurons containing opioid and/or glutamate receptors. Understanding opioid and NMDA receptor targeting during development in the rat model may provide information leading to new approaches for reactivation of developmental plasticity in human brain.
Wang, Hong; Hitron, Ingrid M; Iadecola, Costantino et al. (2005) Synaptic and vascular associations of neurons containing cyclooxygenase-2 and nitric oxide synthase in rat somatosensory cortex. Cereb Cortex 15:1250-60 |
Wang, Hong; Pickel, Virginia M (2004) Activity-regulated cytoskeleton-associated protein Arc is targeted to dendrites and coexpressed with mu-opioid receptors in postnatal rat caudate-putamen nucleus. J Neurosci Res 77:323-33 |
Wang, H; Cuzon, V C; Pickel, V M (2003) Postnatal development of mu-opioid receptors in the rat caudate-putamen nucleus parallels asymmetric synapse formation. Neuroscience 118:695-708 |
Wang, Hong; Cuzon, Verginia C; Pickel, Virginia M (2003) Ultrastructural localization of delta-opioid receptors in the rat caudate-putamen nucleus during postnatal development: relation to synaptogenesis. J Comp Neurol 467:343-53 |