Oxytocin neurons enable social transmission of maternal behaviour.

Maternal care, including by non-biological parents, is important for offspring survival1-8. Oxytocin1,2,9-15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress15. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.

KRAS4A directly regulates hexokinase 1.

The most frequently mutated oncogene in cancer is KRAS, which uses alternative fourth exons to generate two gene products (KRAS4A and KRAS4B) that differ only in their C-terminal membrane-targeting region1. Because oncogenic mutations occur in exons 2 or 3, two constitutively active KRAS proteins-each capable of transforming cells-are encoded when KRAS is activated by mutation2. No functional distinctions among the splice variants have so far been established. Oncogenic KRAS alters the metabolism of tumour cells3 in several ways, including increased glucose uptake and glycolysis even in the presence of abundant oxygen4 (the Warburg effect). Whereas these metabolic effects of oncogenic KRAS have been explained by transcriptional upregulation of glucose transporters and glycolytic enzymes3-5, it is not known whether there is direct regulation of metabolic enzymes. Here we report a direct, GTP-dependent interaction between KRAS4A and hexokinase 1 (HK1) that alters the activity of the kinase, and thereby establish that HK1 is an effector of KRAS4A. This interaction is unique to KRAS4A because the palmitoylation-depalmitoylation cycle of this RAS isoform enables colocalization with HK1 on the outer mitochondrial membrane. The expression of KRAS4A in cancer may drive unique metabolic vulnerabilities that can be exploited therapeutically.

In Vivo Evaluation of Neuronal Transport in Murine Models of Neurodegeneration Using Manganese-Enhanced MRI.

Manganese-enhanced MRI (MRI) is a technique that allows for a noninvasive in vivo estimation of neuronal transport. It relies on the physicochemical properties of manganese, which is both a calcium analogue being transported along neurons by active transport, and a paramagnetic compound that can be detected on conventional T1-weighted images. Here, we report a multi-session MEMRI protocol that helps establish time-dependent curves relating to neuronal transport along the olfactory tract over several days. The characterization of these curves via unbiased fitting enables us to infer objectively a set of three parameters (the rate of manganese transport from the maximum slope, the peak intensity, and the time to peak intensity). These parameters, measured previously in wild type mice during normal aging, have served as a baseline to demonstrate their significant sensitivity to pathogenic processes associated with Tau pathology. Importantly, the evaluation of these three parameters and their use as indicators can be extended to monitor any normal and pathogenic processes where neuronal transport is altered. This approach can be applied to characterize and quantify the effect of any neurological disease conditions on neuronal transport in animal models, together with the efficacy of potential therapies.