We demonstrate the possibility of using carbon nanotubes (CNTs) as potential devices able to improve neural signal transfer while supporting dendrite elongation and cell adhesion. The results strongly suggest that the growth of neuronal circuits on a CNT grid is accompanied by a significant increase in network activity. The increase in the efficacy of neural signal transmission may be related to the specific properties of CNT materials, such as the high electrical conductivity.

The mechanisms underlying the subcellular localization of neurotrophins and their receptors are poorly understood. We show that in cultured hippocampal neurons, the mRNAs for BDNF and TrkB have a somatodendritic localization, and we quantify the extent of their dendritic mRNA localization. In the dendrites the labeling covers on average the proximal 30% of the total dendritic length. On high potassium depolarization, the labeling of BDNF and TrkB mRNA extends on average to 68% of the dendritic length. This increase does not depend on new RNA synthesis, is inhibited by the Na+ channel blocker tetrodotoxin, and involves the activation of glutamate receptors. Extracellular Ca2+, partly flowing through L-type Ca2+ channels, is absolutely required for this process to occur. At the protein level, a brief stimulation of hippocampal neurons with 10 mM KCl leads to a marked increase of BDNF and TrkB immunofluorescence density in the distal portion of dendrites, which also occurs, even if at lower levels, when transport is inhibited by nocodazole. The protein synthesis inhibitor cycloheximide abolishes this increase. The activity-dependent modulation of mRNA targeting and protein accumulation in the dendrites may provide a mechanism for achieving a selective local regulation of the activity of neurotrophins and their receptors, close to their sites of action.

Soluble amyloid-␤ (A␤) peptide is likely to play a key role during early stages of Alzheimer's disease (AD) by perturbing synaptic function and cognitive processes. Receptor for advanced glycation end products (RAGE) has been identified as a receptor involved in A␤-induced neuronal dysfunction. We investigated the role of neuronal RAGE in A␤-induced synaptic dysfunction in the entorhinal cortex, an area of the brain important in memory processes that is affected early in AD. We found that soluble oligomeric A␤ peptide (A␤42) blocked long-term potentiation (LTP), but did not affect long-term depression, paired-pulse facilitation, or basal synaptic transmission. In contrast, A␤ did not inhibit LTP in slices from RAGE-null mutant mice or in slices from wild-type mice treated with anti-RAGE IgG. Similarly, transgenic mice expressing a dominant-negative form of RAGE targeted to neurons showed normal LTP in the presence of A␤, suggesting that neuronal RAGE functions as a signal transducer for A␤-mediated LTP impairment. To investigate intracellular pathway transducing RAGE activation by A␤, we used inhibitors of stress activated kinases. We found that inhibiting p38 mitogen-activated protein kinase (p38 MAPK), but not blocking c-Jun N-terminal kinase activation, was capable of maintaining LTP in A␤-treated slices. Moreover, A␤-mediated enhancement of p38 MAPK phosphorylation in cortical neurons was reduced by blocking antibodies to RAGE. Together, our results indicate that A␤ impairs LTP in the entorhinal cortex through neuronal RAGE-mediated activation of p38 MAPK.