Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice.

The GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice ( ), expressing the "trafficking compromised" GluA1(Q600R) point mutation. Our analysis revealed somatic accumulation and reduction of GluA1(Q600R) and GluA2, but only slightly reduced CA1 synaptic localization in hippocampi of adult mice.

The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development.

Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels.

Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression.

Long-lasting changes in synaptic function are thought to be the cellular basis for learning and memory and for activity-dependent plasticity during development. Long-term potentiation (LTP) and long-term depression (LTD) are two opposing forms of synaptic plasticity that help fine tune neural connections and possibly serve to store information in the brain. Eph receptor tyrosine kinases and their transmembrane ligands, the ephrinBs, have essential roles in certain forms of synaptic plasticity.

Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2.

Apolipoprotein E receptor 2 (Apoer2), a member of the LDL receptor gene family, and its ligand Reelin control neuronal migration during brain development. Apoer2 is also essential for induction of long-term potentiation (LTP) in the adult brain. Here we show that Apoer2 is present in the postsynaptic densities of excitatory synapses where it forms a functional complex with NMDA receptors.

Ecto-nucleotidases and nucleoside transporters mediate activation of adenosine receptors on hippocampal mossy fibers by P2X7 receptor agonist 2'-3'-O-(4-benzoylbenzoyl)-ATP.

The ionotropic and cytolytic P2X7 receptor is typically found on immune cells, where it is involved in the release of cytokines. Recently, P2X7 receptors were reported to be localized to presynaptic nerve terminals and to modulate transmitter release. In the present study, we reassessed this unexpected role of P2X7 receptors at hippocampal mossy fiber-CA3 synapses.

Hippocampal plasticity requires postsynaptic ephrinBs.

Chemical synapses contain specialized pre- and postsynaptic structures that regulate synaptic transmission and plasticity. EphB receptor tyrosine kinases are important molecular components in this process. Previously, EphB receptors were shown to act postsynaptically, whereas their transmembrane ligands, the ephrinBs, were presumed to act presynaptically.

A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A.

In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in size to LTP in wild-type mice at postnatal day 14 (P14) but diminishes between P14 and P42 in brain slices of GluR-A-deficient mice. The GluR-A-independent form of LTP is sensitive to D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), but lacks short-term potentiation (STP) and can also be observed in the pairing induction protocol.