Andrew J. Young

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.

In many animal societies, dominant individuals monopolize reproduction, but the tactics they employ to achieve this are poorly understood. One possibility is that aggressive dominants render their subordinates infertile by inducing chronic physiological "stress." However, this hypothesis has been discarded largely for cooperatively breeding species, where reproductive monopolies are often extreme. Here we provide strong support for the stress-related suppression hypothesis in a cooperative mammal, the meerkat (Suricata suricatta). When pregnant, dominant females subject some subordinate females to escalating aggression, culminating in temporary evictions from the group. While evicted, subordinate females suffer chronic elevation of their glucocorticoid adrenal hormone levels, reproductive down-regulation (reduced pituitary sensitivity to gonadotropin-releasing hormone), reduced conception rates, and increased abortion rates. Rather than constantly harassing all subordinate females, dominants only become aggressive when pregnant themselves (when subordinate reproduction would otherwise conflict with their own) and target those females with whom reproductive conflict is most likely (older, pregnant, and more distantly related females). Our findings suggest that dominant female meerkats employ stressful evictions to suppress reproduction among their probable competitors, when attempting to breed themselves. Given the lack of evidence for stress-related suppression in other cooperative breeders to date, it is clear that social stress alone cannot account for the reproductive failure of subordinates across such societies. However, our findings raise the possibility that, in some cooperative breeders at least, dominants may employ stress-related suppression as a backup mechanism to guard against lapses in reproductive restraint by their subordinates.

In cooperatively breeding birds, where helpers of both sexes assist with the provisioning and upbringing of offspring who are not their own, males tend to contribute more than females to rearing young. This sex difference has been attributed to paternity uncertainty, but could also occur because males contribute more where they are likely to remain and breed in their group of origin. In contrast to most birds, female meerkats (Suricata suricatta) are more likely to breed in their natal group than males. We show that female meerkat helpers contribute more to rearing young than males and that female helpers feed female pups more frequently than males. Our results suggest that sex differences in cooperative behavior are generated by sex differences in philopatry and occur because females derive greater direct benefits than males from raising recruits to their natal group. These findings support the view that direct, mutualistic benefits are important in the evolution of specialized cooperative behavior.

Evolutionary biology and biomedicine have seen a surge of recent interest in the possibility that telomeres play a role in life-history trade-offs and ageing. Here, I evaluate alternative hypotheses for the role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing, and highlight outstanding challenges. First, while recent findings underscore the possibility of a proximate causal role for telomeres in current-future trade-offs and ageing, it is currently unclear (i) whether telomeres ever play a causal role in either and (ii) whether any causal role for telomeres arises via shortening or length-independent mechanisms. Second, I consider why, if telomeres do play a proximate causal role, selection has not decoupled such a telomere-mediated trade-off between current and future performance. Evidence suggests that evolutionary constraints have not rendered such decoupling impossible. Instead, a causal role for telomeres would more plausibly reflect an adaptive strategy, born of telomere maintenance costs and/or a function for telomere attrition (e.g. in countering cancer), the relative importance of which is currently unclear. Finally, I consider the potential for telomere biology to clarify the constraints at play in life-history evolution, and to explain the form of the current-future trade-offs and ageing trajectories that we observe today.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system's versatility.