A noncanonical postsynaptic transport route for a GPCR belonging to the serotonin receptor family.

Postsynaptic receptor trafficking plays an essential role in tuning neurotransmission and signal plasticity and has emerged as a potential therapeutic target in neuropsychiatric disease. Using a novel application of fluorescence recovery after photobleaching in rat hippocampal neurons, we examined transport from the soma to dendrites of seven G-protein-coupled receptors (GPCRs) implicated in mood disorders. Most GPCRs were delivered to dendrites via lateral diffusion, but one GPCR, the serotonin 1B receptor (5-HT(1B)), was delivered to the dendrites in secretory vesicles. Within the dendrites, 5-HT(1B) were stored in a reservoir of accessible vesicles that were recruited to preferential sites in plasma membrane, as observed with superecliptic pHluorin labeling. After membrane recruitment, 5-HT(1B) transport via lateral diffusion and temporal confinement to inhibitory and excitatory synapses was monitored by single particle tracking. These results suggest an alternative mechanism for control of neuronal activity via a GPCR that has been implicated in mood regulation.

Effect of TNF-alpha on CD3-zeta and MHC-I in postnatal rat hippocampus.

The zeta subunit of the CD3 T-cell receptor complex and the major histocompatibility complex class 1 (MHC-I) are important not only for the immune response to antigens, they also function as signal molecules in the brain, where they play a role in the postnatal maturation process. The expression of these molecules can be regulated by cytokines. In situations associated with increased cytokine production, such as neonatal hypoxia, the hippocampus is particularly susceptible to permanent damage. This has prompted us to examine the MHC-I and CD3-zeta expression in hippocampus from early postnatal, weanling and adolescent rats and to record the effects of TNF-alpha and IL-1beta, cytokines commonly increased in neonatal hypoxia, on MHC-I and CD3-zeta expression in the hippocampus. We show that there is a robust postnatal up-regulation of CD3-zeta and MHC-I protein as well as of MHC-I mRNA and that TNF-alpha down-regulates the expression of CD3-zeta protein and MHC-I mRNA in early postnatal but not in weanling nor in adolescent rats. These results may offer a molecular explanation to the adverse effects of increased circulating levels of cytokines on brain in neonatal hypoxia.