Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility

The biological basis of the increased risk for psychiatric disorders seen in 15q11.2 copy number deletion is unknown. Previous work has shown disturbances in white matter tracts in human carriers of the deletion. Here, in a novel rat model, we recapitulated low dosage of the candidate risk gene CYFIP1 present within the 15q11.2 interval. Using diffusion tensor imaging, we first showed extensive white matter changes in Cyfip1 mutant rats, which were most pronounced in the corpus callosum and external capsule. Transmission electron microscopy showed that these changes were associated with thinning of the myelin sheath in the corpus callosum. Myelin thinning was independent of changes in axon number or diameter but was associated with effects on mature oligodendrocytes, including aberrant intracellular distribution of myelin basic protein. Finally, we demonstrated effects on cognitive phenotypes sensitive to both disruptions in myelin and callosal circuitry

The Nucleus Accumbens: A Switchboard for Goal-Directed Behaviors

Reward intake optimization requires a balance between exploiting known sources of rewards and exploring for new sources. The prefrontal cortex (PFC) and associated basal ganglia circuits are likely candidates as neural structures responsible for such balance, while the hippocampus may be responsible for spatial/contextual information. Although studies have assessed interactions between hippocampus and PFC, and between hippocampus and the nucleus accumbens (NA), it is not known whether 3-way interactions among these structures vary under different behavioral conditions. Here, we investigated these interactions with multichannel recordings while rats explored an operant chamber and while they performed a learned lever-pressing task for reward in the same chamber shortly afterward. Neural firing and local field potentials in the NA core synchronized with hippocampal activity during spatial exploration, but during lever pressing they instead synchronized more strongly with the PFC. The latter is likely due to transient drive of NA neurons by bursting prefrontal activation, as in vivo intracellular recordings in anesthetized rats revealed that NA up states can transiently synchronize with spontaneous PFC activity and PFC stimulation with a bursting pattern reliably evoked up states in NA neurons. Thus, the ability to switch synchronization in a task-dependent manner indicates that the NA core can dynamically select its inputs to suit environmental demands, thereby contributing to decision-making, a function that was thought to primarily depend on the PFC

Growth Hormone Promotes Hair Cell Regeneration in the Zebrafish (Danio rerio) Inner Ear following Acoustic Trauma

BACKGROUND: Previous microarray analysis showed that growth hormone (GH) was significantly upregulated following acoustic trauma in the zebrafish (Danio rerio) ear suggesting that GH may play an important role in the process of auditory hair cell regeneration. Our objective was to examine the effects of exogenous and endogenous GH on zebrafish inner ear epithelia following acoustic trauma. METHODOLOGY/PRINCIPAL FINDINGS: We induced auditory hair cell damage by exposing zebrafish to acoustic overstimulation. Fish were then injected intraperitoneally with either carp GH or buffer, and placed in a recovery tank for either one or two days. Phalloidin-, bromodeoxyuridine (BrdU)-, and TUNEL-labeling were used to examine hair cell densities, cell proliferation, and apoptosis, respectively. Two days post-trauma, saccular hair cell densities in GH-treated fish were similar to that of baseline controls, whereas buffer-injected fish showed significantly reduced densities of hair cell bundles. Cell proliferation was greater and apoptosis reduced in the saccules, lagenae, and utricles of GH-treated fish one day following trauma compared to controls. Fluorescent in situ hybridization (FISH) was used to examine the localization of GH mRNA in the zebrafish ear. At one day post-trauma, GH mRNA expression appeared to be localized perinuclearly around erythrocytes in the blood vessels of the inner ear epithelia. In order to examine the effects of endogenous GH on the process of cell proliferation in the ear, a GH antagonist was injected into zebrafish immediately following acoustic trauma, resulting in significantly decreased cell proliferation one day post-trauma in all three zebrafish inner ear end organs. CONCLUSIONS/SIGNIFICANCE: Our results show that exogenous GH promotes post-trauma auditory hair cell regeneration in the zebrafish ear through stimulating proliferation and suppressing apoptosis, and that endogenous GH signals are present in the zebrafish ear during the process of auditory hair cell regeneration

Methodological strategies to understand smartphone practices for social connectedness in later life

Digital practices in later life are not yet well understood. Therefore, this paper discusses the framework for a research design project that aims at tracing differences and similarities in how older adults use their smartphones in circumstances in and outside their homes in Spain, the Netherlands, Sweden, and Canada. The research questions of this international research project focus on the extent to which digital mobile practices relate to perceived social connectedness among older adults aged 55–79 years old. While studies have shown that the subjective experience of ‘being connected’ supports continued wellbeing in later life, there remains an insufficient understanding of the processes through which digital mediated social interaction is effective for social connectedness. The analytical framework of the project prioritizes the co-constituency of (digital) technology and ageing, and takes digital practices in everyday life as its entry point. The main data collection tool will be the tracking of smartphone activity of 600 older adults (150 per country) during four weeks. An online survey and qualitative interviews will gather data about the meanings of the quantified digital practices, and how they shape (if they do) the participants’ connection to the world. This approach will allow us not only to get insight into what older adults say how they used their smartphone but also to gain insight into their real-life daily use. The assessment of the challenges, strengths, and weaknesses of the methods contributes towards an accurate and appropriate interpretation of empirical results and their implications