Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization.

N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activity regulates the net number of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR) at the cell surface by modulating the balance between AMPAR membrane insertion and endocytosis. In this study, we addressed the role of NMDAR subtypes and of NMDAR-mediated Ca2+ influx in the NMDAR-induced endocytosis of GluR2-containing AMPARs in primary murine hippocampal neurons. We found that NMDAR activation enhanced the endocytosis of AMPARs containing the GluR2 splice variants with short, but not long, cytoplasmic tails. NMDA-induced GluR2 endocytosis was completely inhibited by pharmacological block of NR2B-containing NMDARs. In turn, preferential block of NR2A-containing NMDARs did not affect NMDA-induced AMPAR endocytosis, indicating that AMPAR internalization is controlled by a restricted set of NMDARs. The NMDA-induced GluR2 internalization was also observed in the absence of extracellular Na+ ions, suggesting that membrane depolarization is not a prerequisite for this effect. Furthermore, the activation of Ca2+-impermeable NMDARs containing the mutant NR1(N598R) subunit failed to enhance AMPAR endocytosis, indicating a requirement of Ca2+ influx directly through the NMDAR channels. In summary, our findings suggest that the NMDAR-induced selective internalization of short C-terminal GluR2-containing AMPARs requires a Ca2+ signal that originates from NMDAR channels and is processed in an NMDAR subtype-restricted manner.

Insect mouthpart motor patterns: central circuits modified for highly derived appendages?

The interrelationships of motor patterns controlling the mouthparts and the salivary gland of the migratory locust were studied in a deafferented preparation activated by the muscarinic agonist pilocarpine. The aim of the study was to check whether motor output of different neuromeres of the suboesophageal ganglion and the brain is coherent and functionally adequate in the absence of sensory feedback. Our analysis shows that motor output to labial, maxillar, and labral muscles and to the salivary gland is strongly coupled to the mandibular motor pattern. Bilateral coupling is of similar strength. For a muscle of the labial palp, however, an independent pattern is shown. From our findings it is concluded that for stable coordination of most muscles involved in mouthpart movements sensory feedback is not essential. This is in contrast to motor patterns controlling thoracic appendages in similar insect model systems. As mouthparts are widely accepted to be homologous to thoracic appendages, it is concluded that during the evolutionary process which led to derived features of mouthparts also the central nervous networks controlling these structures were reconfigured accordingly.

Nitric oxide induces centrally generated motor patterns in the locust suboesophageal ganglion.

The stimulatory effects of nitric oxide (NO) on central motor pattern generation in isolated locust suboesophageal ganglia (SOGs) were studied using extracellular recordings from motor nerves. Different NO donor molecules and a specific inhibitor of soluble guanylyl cyclases were used to confirm that the observed motor pattern occurred in response to activation of the NO/cyclic GMP signalling pathway. Experiments with muscarinic agonists and antagonists showed that the NO-induced motor pattern is generated independently from the motor pattern induced by muscarinic agonists described previously. Staining for NADPH-diaphorase and an antiserum directed against cyclic GMP were used to identify neurones representing potential sources of NO and their target cells within the SOG. Using intracellular dye injection and backfilling of peripheral nerves in combination with anti-cGMP immunohistochemistry, it was shown that identified efferent neurones involved in the mandibular motor pattern are potential target cells of NO.