Neuroscience
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AMPA receptors have been identified in different populations of presynaptic terminals and found to be involved in the modulation of neurotransmitter release. The mechanisms that govern the expression of presynaptic AMPA receptors are not known. One possibility is that pre- and postsynaptic AMPA receptors are regulated according to the same principles. ⋯ Subfractionation and high-resolution immunogold analyses of the rat hippocampus revealed that GluR2 and PICK1 are enriched postsynaptically, but also in presynaptic membrane compartments, including the active zone and vesicular membranes. PICK1 and GluR2 are associated with the same vesicles, which are immunopositive also for synaptophysin and vesicle-associated membrane protein 2. Based on what is known about the function of PICK1 postsynaptically, the present data suggest that PICK1 is involved in the regulation of presynaptic AMPA receptor trafficking and in determining the size of the AMPA receptor pool that modulates presynaptic glutamate release.
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Functional evidence suggests that neuronal enriched endosomal protein of 21 kDa (NEEP21) takes part in facilitating transport of AMPA receptors (AMPAR) in the synapse. To explore the anatomical basis for a role in this synaptic trafficking, we investigated the ultrastructural localization of NEEP21 in rodent brain. Using immunogold electron microscopy, we show that NEEP21 is colocalized with the AMPAR subunits GluR2/3 in postsynaptic spines. ⋯ NEEP21 positive endosomes/multivesicular bodies were found throughout cell bodies and dendrites. In light microscopical preparations, the NEEP21 antibody produced a labeling pattern in the neocortex, hippocampus and cerebellum that mimicked that of GluR2/3 and not that of GluR1 or 4. Our findings are consistent with a role for NEEP21 in facilitating vesicular transport of GluR2 between intracellular compartments and the postsynaptic plasma membrane.
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Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioural disorder among children. ADHD children are hyperactive, impulsive and have problems with sustained attention. These cardinal features are also present in the best validated animal model of ADHD, the spontaneously hypertensive rat (SHR), which is derived from the Wistar Kyoto rat (WKY). ⋯ This indicates that the SHR has a functional predominance of NR2B, a feature characteristic of early developmental stages in these synapses. Quantitative immunofluorescence and electron microscopic postembedding immunogold cytochemistry of the three major NMDAR subunits (NR1, NR2A; and NR2B) in stratum radiatum spine synapses revealed no differences between SHR and WKY. The results indicate that functional impairments in glutamatergic synaptic transmission may be one of the underlying mechanisms leading to the abnormal behavior in SHR, and possibly in human ADHD.