Activity

Visuomotor transformations at the cortical level occur along a network where posterior parietal regions are connected to homologous premotor regions. Grasping-related activity is represented in a diffuse, ventral and dorsal system in the posterior parietal regions, but no systematic causal description of a premotor counterpart of a similar diffuse grasping representation is available. To fill this gap, we measured the kinematics of right finger movements in 17 male and female human participants during grasping of three objects of different sizes. Single-pulse transcranial magnetic stimulation was applied 100 ms after visual presentation of the object over a regular grid of 8 spots covering the left premotor cortex (PMC) and 2 Sham stimulations. Maximum finger aperture during reach was used as the feature to classify object size in different types of classifiers. Classification accuracy was taken as a measure of the efficiency of visuomotor transformations for grasping. Results showed that transcranial magnetig the fingers according to the size of the target. Crucially, we found that the medial part of PMC, putatively covering the supplementary motor area, plays a direct role in object grasping. In concert with findings in nonhuman primates, these results indicate a multifocal representation of object geometry for grasping in the PMC and expand our understanding of how our brain integrates visual and motor information to perform visually guided actions.A reduction in the synthesis of the neuromodulator histamine has been associated with Tourette’s syndrome and obsessive-compulsive disorder. Symptoms of these disorders are thought to arise from a dysfunction or aberrant development ofcorticostriatal circuits. Here, we investigated how histamine affects developing corticostriatal circuits, both acutely and longer-term, during the first postnatal weeks, using patch-clamp and field recordings in mouse brain slices (C57Bl/6, male and female). Immunohistochemistry for histamine-containing axons reveals striatal histaminergic innervation by the second postnatal week, and qRT-PCR shows transcripts for H1, H2, and H3 histamine receptors in striatum from the first postnatal week onwards, with pronounced developmental increases in H3 receptor expression. selleck chemical Whole-cell patch-clamp recordings of striatal spiny projection neurons and histamine superfusion demonstrates expression of functional histamine receptors from the first postnatal week onwards, with histamine having dic disorders, although rare, can provide opportunities to both study and understand the brain. For example, a nonsense mutation in the coding gene for the histamine-synthesizing enzyme has been associated with Tourette’s syndrome and obsessive-compulsive disorder, and dysfunction of corticostriatal circuits. Nevertheless, the etiology of these neurodevelopmental disorders and histamine’s role in the development of corticostriatal circuits have remained understudied. Here we show that histamine is an active neuromodulator during the earliest periods of postnatal life and acts at developing striatal neurons and synapses. Crucially, we show that histamine permits NMDA receptor-dependent corticostriatal synaptic plasticity during an early critical period of postnatal development, which suggests that genetic or environmental perturbations of histamine levels can impact striatal development.Radial glial progenitors in the mammalian developing neocortex have been shown to follow a deterministic differentiation program restricted to an asymmetric-only mode of division. This feature seems incompatible with their well-known ability to increase in number when cultured in vitro, driven by fibroblast growth factor 2 and other mitogenic signals. The changes in their differentiation dynamics that allow this transition from in vivo asymmetric-only division mode to an in vitro self-renewing culture have not been fully characterized. Here, we combine experiments of radial glia cultures with numerical models and a branching process theoretical formalism to show that fibroblast growth factor 2 has a triple effect by simultaneously increasing the growth fraction, promoting symmetric divisions and shortening the length of the cell cycle. These combined effects partner to establish and sustain a pool of rapidly proliferating radial glial progenitors in vitro We also show that, in conditions of variable proliferation dynamics, the branching process tool outperforms other commonly used methods based on thymidine analogs, such as BrdU and EdU, in terms of accuracy and reliability.Cell death is an important facet of animal development. In some developing tissues, death is the ultimate fate of over 80% of generated cells. Although recent studies have delineated a bewildering number of cell death mechanisms, most have only been observed in pathological contexts, and only a small number drive normal development. This Primer outlines the important roles, different types and molecular players regulating developmental cell death, and discusses recent findings with which the field currently grapples. We also clarify terminology, to distinguish between developmental cell death mechanisms, for which there is evidence for evolutionary selection, and cell death that follows genetic, chemical or physical injury. Finally, we suggest how advances in understanding developmental cell death may provide insights into the molecular basis of developmental abnormalities and pathological cell death in disease.Asthma is the most common chronic condition of childhood. In this review, we discuss an overview of strategies to empower children and young people with asthma. The key aspects of empowerment are to enable shared decision making and self-management, and help children minimise the impact of asthma on their life. The evidence behind these strategies is either sparse or heterogenous, and it is difficult to identify which interventions are most likely to improve clinical outcomes. Wider determinants of health, in high-resource and low-resource settings, can be disempowering for children with asthma. New approaches to technology could help empower young people with asthma and other chronic health conditions.