Stuber, G. D., Sparta, D. R., Stamatakis, A. M., van Leeuwen, W. A., Hardjoprajitno, J. E., Cho, S., et al. (2011). Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature, advance online publication.
Abstract: The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence1, 2, 3, 4, 5, 21, 22, 23. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours4, 6, 7, 24, 25, but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.
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Ramsden, S., Richardson, F. M., Josse, G., Thomas, M. S. C., Ellis, C., Shakeshaft, C., et al. (2011). Verbal and non-verbal intelligence changes in the teenage brain. Nature, advance online publication.
Abstract: Intelligence quotient (IQ) is a standardized measure of human intellectual capacity that takes into account a wide range of cognitive skills1. IQ is generally considered to be stable across the lifespan, with scores at one time point used to predict educational achievement and employment prospects in later years1. Neuroimaging allows us to test whether unexpected longitudinal fluctuations in measured IQ are related to brain development. Here we show that verbal and non-verbal IQ can rise or fall in the teenage years, with these changes in performance validated by their close correlation with changes in local brain structure. A combination of structural and functional imaging showed that verbal IQ changed with grey matter in a region that was activated by speech, whereas non-verbal IQ changed with grey matter in a region that was activated by finger movements. By using longitudinal assessments of the same individuals, we obviated the many sources of variation in brain structure that confound cross-sectional studies. This allowed us to dissociate neural markers for the two types of IQ and to show that general verbal and non-verbal abilities are closely linked to the sensorimotor skills involved in learning. More generally, our results emphasize the possibility that an individual’s intellectual capacity relative to their peers can decrease or increase in the teenage years. This would be encouraging to those whose intellectual potential may improve, and would be a warning that early achievers may not maintain their potential.
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Potts, W. K., Manning, C. J., & Wakeland, E. K. (1991). Mating patterns in seminatural populations of mice influenced by MHC genotype. Nature, 352(6336), 619–621.
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Barton, N. (1998). Evolutionary biology: The geometry of adaptation. Nature, 395(6704), 751–752.
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Chittka, L., & Dyer, A. (2012). Cognition: Your face looks familiar. Nature, 481(7380), 154–155.
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Apicella, C. L., Marlowe, F. W., Fowler, J. H., & Christakis, N. A. (2012). Social networks and cooperation in hunter-gatherers. Nature, 481(7382), 497–501.
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Ferrero, D. M., Moeller, L. M., Osakada, T., Horio, N., Li, Q., Roy, D. S., et al. (2013). A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Nature, 502(7471), 368–371.
Abstract: Animals display a repertoire of different social behaviours. Appropriate behavioural responses depend on sensory input received during social interactions. In mice, social behaviour is driven by pheromones, chemical signals that encode information related to age, sex and physiological state1. However, although mice show different social behaviours towards adults, juveniles and neonates, sensory cues that enable specific recognition of juvenile mice are unknown. Here we describe a juvenile pheromone produced by young mice before puberty, termed exocrine-gland secreting peptide 22 (ESP22). ESP22 is secreted from the lacrimal gland and released into tears of 2- to 3-week-old mice. Upon detection, ESP22 activates high-affinity sensory neurons in the vomeronasal organ, and downstream limbic neurons in the medial amygdala. Recombinant ESP22, painted on mice, exerts a powerful inhibitory effect on adult male mating behaviour, which is abolished in knockout mice lacking TRPC2, a key signalling component of the vomeronasal organ2, 3. Furthermore, knockout of TRPC2 or loss of ESP22 production results in increased sexual behaviour of adult males towards juveniles, and sexual responses towards ESP22-deficient juveniles are suppressed by ESP22 painting. Thus, we describe a pheromone of sexually immature mice that controls an innate social behaviour, a response pathway through the accessory olfactory system and a new role for vomeronasal organ signalling in inhibiting sexual behaviour towards young. These findings provide a molecular framework for understanding how a sensory system can regulate behaviour.
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Moon, C., Baldridge, M. T., Wallace, M. A., Burnham, C. - A. D., Virgin, H. W., & Stappenbeck, T. S. (2015). Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature, 521(7550), 90–93.
Abstract: The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control1-5. In many cases, the microbiota is the presumed culprit of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice6,7. In conventionally raised mice, the microbiome is transmitted from the dam2,8,9. Here we show that microbially–driven dichotomous fecal IgA levels in WT mice within the same facility mimic the effects of chromosomal mutations. We observed in multiple facilities that vertically-transmissible bacteria in IgA-Low mice dominantly lowered fecal IgA levels in IgA-High mice after cohousing or fecal transplantation. In response to injury, IgA-Low mice showed increased damage that was transferable by fecal transplantation and driven by fecal IgA differences. We found that bacteria from IgA-Low mice degraded the secretory component (SC) of SIgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose fecal IgA as one marker of microbial variability and conclude that cohousing and/or fecal transplantation enables analysis of progeny from different dams.
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