RESEARCH HIGHLIGHTS LEARNING AND MEMORY Increases in intracellular Ca2+ induce long-term changes in synaptic strength through the activation of CREB (cyclic AMP responsive element (CRE) binding protein), Reelin’ in clues to memory which triggers changes in gene transcription and expression. In the presence of Reelin, Reelin is well known to regulate neuronal for NMDAR gating activity. It turns out that glutamate induced phosphorylation of migration in embryonic development. More DAB1 activates Src family kinases (SFKs), CREB, whereas glutamate or Reelin alone recently, it has been implicated in long-term which are crucial for phosphorylation had only minor effects. This indicates that potentiation in the adult hippocampus. of NMDAR subunits. This suggests the Reelin might, ultimately, influence long-term New work, reported in The Journal of intriguing possibility of a relationship synaptic plasticity by modulating activity- Neuroscience, shows that this dual role for between the Reelin-activated developmental dependent gene transcription through its Reelin in development and memory involves signalling pathway and the regulation of influence on intracellular Ca2+ concentrations. a shared signalling pathway that influences synaptic ion channels. This work draws together several lines of memory through its regulation of NMDA To test this possibility, Chen and evidence to support a modulatory role for (N-methyl-d-aspartate) receptor function. colleagues investigated the effects of Reelin in long-term synaptic plasticity in During embryonic development, Reelin on Ca2+ influx through NMDARs adulthood through its effects on NMDAR Reelin regulates the proper positioning in primary cortical neurons of rats and gating. Moreover, results indicate that of neurons by triggering a cascade of mice. In the presence of Reelin, glutamate the same Reelin-activated developmental events, starting with its binding to the very stimulation led to a striking increase in Ca2+ signalling pathway that supports neuronal low-density lipoprotein (VLDL) receptor influx through NMDARs, whereas Reelin migration is central to its role in learning (VLDLR) and apolipoprotein E receptor 2 or glutamate stimulation alone led to no and memory. (APOER2), which, in turn, induces tyrosine such increase. Blocking Reelin binding Alison Rowan phosphorylation of the adaptor protein to VLDLR and APOER2 prevented the disabled 1 (DAB1). enhancing effects of glutamate-mediated References and links ORIGINAL RESEARCH PAPER Chen, Y. et al. Reelin 2+ NMDA receptors (NMDARs) modulate Ca influx. A similar effect was observed modulates NMDA receptor activity in cortical neurons. synapse formation and long-term changes in neurons that were deficient in DAB1, J. Neurosci. 25, 8209–8216 (2005) in synaptic strength through their control and, therefore, unable to respond to Reelin. FURTHER READING Tissir, F. & Goffinet, A. M. Reelin and 2+ brain development. Nature Rev. Neurosci. 4, 496–505 (2005) | of Ca entry into neurons. Phosphorylation Pharmacological inhibition of SFKs also Beffert, U. et al. Modulation of synaptic plasticity and memory and dephosphorylation of tyrosine residues abolished the enhancing effects of Reelin on by Reelin involves differential splicing of the lipoprotein on NR2 subunits of NMDARs is necessary Ca2+ influx. receptor Apoer2. Neuron 47, 567–570 (2005) ION CHANNELS Xu and colleagues now report that camphor activates TRPV1 in a manner that is independent of the vanilloid (capsaicin) The comfort of camphor binding site, and inhibits ankyrin-repeat TRP 1 (TRPA1). Both of these thermoTRPs The analgesic properties of camphor, a plant- The six subfamilies of TRP ion chan- are abundant in nociceptive dorsal root derived product with a long history of medical nels have diverse roles as cellular sensors. ganglion (DRG) neurons. Camphor-evoked use, might reflect its effects on at least two Thermosensitive TRP channels detect a TRPV1-like currents recorded from rat DRG types of TRP (transient receptor potential) wide range of temperatures, including cool neurons were strongly potentiated after a ion channel, according to a recent report from and warmth, and noxious cold and heat. In manipulation that mimicked peripheral David Clapham’s laboratory. addition, all thermoTRP channels seem to sensitization, which suggests that the use of be chemosensitive. For example, the vanil- camphor to treat irritated or inflamed skin loid receptor TRPV1 is stimulated by heat might be related to its increased efficacy in and by capsaicin (the ‘hot’ ingredient in these states. chilli peppers), the analgesic effects of which Among TRPV1 agonists, Xu et al. showed are probably due, at least in part, to channel that camphor has exceptionally strong desen- desensitization. sitizing properties. The combined desensiti- Camphor is commonly applied to the zation of TRPV1 and inhibition of TRPA1 skin for analgesic, antipruritic and coun- provides a new explanation for the analgesic ter-irritant purposes, but its molecular and properties of this age-old remedy. cellular targets are largely unknown. Camphor Rebecca Craven was recently shown to activate TRPV3 in References and links epithelial keratinocytes, and is known to pro- ORIGINAL RESEARCH PAPER Xu, H. et al. Camphor activates and strongly desensitizes the transient receptor duce a warm sensation, in keeping with the potential vanilloid subtype 1 channel in a vanilloid- thermal activation range of this thermoTRP. independent mechanism. J. Neurosci. 25, 8924–8937 But repeated applications of camphor led to (2005) FURTHER READING Moqrich, A. et al. Impaired TRPV3 sensitization, apparently contradicting thermosensation in mice lacking TRPV3, a heat and camphor’s analgesic role. camphor sensor in the skin. Science 307, 1468–1472 (2005) 826 | NOVEMBER 2005 | VOLUME 6 www.nature.com/reviews/neuro.