Myelin-associated glycoprotein (MAG), an inhibitor of axon regeneration, binds with high affinity to the Nogo-66 receptor (NgR). Here we report that the p75 neurotrophin receptor (p75(NTR)) is a co-receptor of NgR for MAG signaling. In cultured human embryonic kidney (HEK) cells expressing NgR, p75(NTR) was required for MAG-induced intracellular Ca2+ elevation. Co-immunoprecipitation showed an association of NgR with p75(NTR) that can be disrupted by an antibody against p75(NTR) (NGFR5), and extensive coexpression was observed in the developing rat nervous system. Furthermore, NGFR5 abolished MAG-induced repulsive turning of Xenopus axonal growth cones and Ca2+ elevation, both in neurons and in NgR/p75(NTR)-expressing HEK cells. Thus we conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration.

We report measurement of the OH librational band in nanoscopic pools of water and methanol confined within reverse micelles. The librational band, which peaks near 670 cm-1 in the bulk liquids, shifts to lower frequency as the reverse micelle size decreases. In addition, the shape of the band changes considerably as a function of decreasing size. The librational band at all compositions is well fit by a two-state model based on the relative fractions of bound and free water (or methanol) within the reverse micelles.

We found a high prevalence of comorbid conditions among individuals with AA presenting to academic medical centers in Boston. Physicians caring for patients with AA should consider screening for comorbid conditions.

The performance of developing zebrafish in both classical and operant conditioning assays was tested with a particular focus on the emergence of these learning behaviors during development. Strategically positioned visual cues paired with electro-shocks were used in two fully automated assays to investigate both learning paradigms. These allow the evaluation of the behavioral performance of zebrafish continuously throughout development, from larva to adult. We found that learning improves throughout development, starts reliably around week 3, and reaches adult performance levels at week 6. Adult fish quickly learned to perform perfectly, and the expression of the learned behavior is manifestly controlled by vision. The memory is behaviorally expressed in adults for at least 6 h and retrievable for at least 12 h. [Supplemental material is available for this article.] The ability to associate two environmental cues, as in classical conditioning, or to correlate one's behavior with its consequences , as in operant conditioning, are processes often essential for an animal's survival (Skinner 1984). While there are studies that have followed the ontogeny of learning behaviors in animal model systems of classical conditioning paradigms (Campbell and Ampuero 1985; Moye and Rudy 1985; Paczkowski et al. 1999; Raineki et al. 2009), the ontogeny of operant learning, in particular , remains much less explored. The ability for classical conditioning is pervasive across the animal kingdom and often interpreted as the most basic and robust form of associative learning; however, it has been shown that adding an operant component to a learning task may increase performance, or show it where it was not present before (Heisen-berg et al. 2001; Moore 2004). Zebrafish is an exceptional model of vertebrate neural development and amenable both to forward genetics and genetic manipulation (Neuhauss 2003). The transparent larvae are uniquely suited to functional imaging and have recently served to uncover fundamental mechanisms in fish locomotor control (Orger et al. 2008; Portugues and Engert 2009). Behavior is the ultimate functional readout of neural activity; indeed, behavior is the ultimate evolutionary reason for the existence of brains and the changes in behavior during development should reflect the changes the nervous system undergoes as the larval organism develops into the adult. While there are well-established learning paradigms for Drosophila and rodent experimental models, zebra-fish still lacks a systematic learning characterization. We describe here an approach to implement and test such a learning assay that utilizes the fact that zebrafish can see and track visual stimuli and clearly perform visually evoked locomotor behaviors as early as 5 d post-fertilization (dpf) (Easter and Nicola 1996; Budick and O'Malley 2000). To that end we use visually guided stimuli combined with a noxious electroshock to control learning behaviors. We characterize these assays and specifically obtain a full ontoge-ny of operant learning fr...