The molecular mechanisms that regulate basal or background entry of divalent cations into mammalian cells are poorly understood. Here we describe the cloning and functional characterization of a Ca2+- and Mg2+-permeable divalent cation channel, LTRPC7 (nomenclature compatible with that proposed in ref. 1), a new member of the LTRPC family of putative ion channels. Targeted deletion of LTRPC7 in DT-40 B cells was lethal, indicating that LTRPC7 has a fundamental and nonredundant role in cellular physiology. Electrophysiological analysis of HEK-293 cells overexpressing recombinant LTRPC7 showed large currents regulated by millimolar levels of intracellular Mg.ATP and Mg.GTP with the permeation properties of a voltage-independent divalent cation influx pathway. Analysis of several cultured cell types demonstrated small magnesium-nucleotide-regulated metal ion currents (MagNuM) with regulation and permeation properties essentially identical to the large currents observed in cells expressing recombinant LTRPC7. Our data indicate that LTRPC7, by virtue of its sensitivity to physiological Mg.ATP levels, may be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell.

The high affinity receptor for immunoglobulin E (designated Fc epsilon RI) is the member of the antigen (Ag) receptor superfamily responsible for linking pathogen-or allergen-specific IgEs with cellular immunologic effector functions. This review provides background information on Fc epsilon RI function combined with more detailed summaries of recent progress in understanding specific aspects of Fc epsilon RI biology and biochemistry. Topics covered include the coordination and function of the large multiprotein signaling complexes that are assembled when Fc epsilon RI and other Ag receptors are engaged, new information on human receptor structures and tissue distribution, and the role of the FcR beta chain in signaling and its potential contribution to atopic phenotypes.

Fear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Ca v 1.2 Ca 2+ channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Ca v 1.2 channels of the ACC in observational social fear.Fear is a biological response to dangerous, threatening situations or stimuli. Fear can be acquired and expressed in a variety of ways 1 . First, fear can be learned from direct experience of an adverse situation (for example, an unconditioned stimulus in classical Pavlovian fear conditioning). In a classical conditioning experiment, pairing of a neutral, conditioned stimulus (for example, a tone) with an aversive, unconditioned stimulus (for example, a foot shock) causes an animal to express fear behaviors when the animal is later exposed to the conditioned Correspondence should be addressed to H.-S.S. (shin@kist.re.kr). 6 Present address: Department of Neurology, Seoul National University Hospital, Seoul, Korea.Note: Supplementary information is available on the Nature Neuroscience website. AUTHOR CONTRIBUTIONS COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests.Reprints and permissions information is available online at http://www.nature.com/reprintsandpermissions/. 1,[6][7][8][9][10][11][12] . Previous studies using a barpressing protocol found that rats seeing a distressed conspecific (by electric shocks) display fearful behavioral responses, such as crouching or motionlessness 13,14 . A recent study found that C57BL/6J mice that observed unfamiliar mice experiencing classical fear conditioning displayed freezing behaviors when they were later exposed to the conditioned stimulus alone 15 . These findings demonstrate social transfer of fear in rodents. Unlike classical fear conditioning, however, the neural substrate and mechanism underlying observational social fear has not been well defined. NIH Public AccessACC is known to receive sensory signals from the somatosensory cortices and other cortical areas, including the anterior insular cortex [16][17][18][19][20] . Brain-imaging studies in humans have shown that the neuronal activities of the ACC and the amygdala change during observation of others experi...