GABA-A receptor-dependent mechanisms prevent excessive spine elimination during postnatal maturation of the mouse cortex in vivo

Dendritic spine dynamics are implicated in the structural plasticity of cognition-related neuroconnectivity. This study utilized the transcranial in vivo imaging approach to investigate spine dynamics in intact brains of living yellow fluorescent protein-expressing mice. A developmental switch in the net spine loss rate occurred at ∼4 months of age. The initially rapid rate slowed down ∼6-fold due to substantially reduced spine elimination with minor changes in formation. Furthermore, pharmacological blockade of γ-aminobutyric acid type A (GABA-A) receptors resulted in significantly increased elimination of pre-existing spines without affecting new spine formation. Spine elimination returned to normal levels following treatment cessation. Thus, GABA-A receptor-dependent mechanisms act as “brakes” – keeping spine elimination in check to prevent over-pruning, thereby preserving the integrity of cognition-related cortical circuits.     

The shape and mobility of the thoracic spine in asymptomatic adults – A systematic review of in vivo studies

A comprehensive knowledge of the thoracic shape and kinematics is essential for effective risk prevention, diagnose and proper management of thoracic disorders and assessment of treatment or rehabilitation strategies as well as for in silico and in vitro models for realistic applications of boundary conditions.After an extensive search of the existing literature, this study summarizes 45 studies on in vivo thoracic kyphosis and kinematics and creates a systematic and detailed database. The thoracic kyphosis over T1–12 determined using non-radiological devices (34°) was relatively less than measured using radiological devices (40°) during standing. The majority of kinematical measurements are based on non-radiological devices. The thoracic range of motion (RoM) was greatest during axial rotation (40°), followed by lateral bending (26°), and flexion (21°) when determined using non-radiological devices during standing. The smallest RoM was identified during extension (13°). The lower thoracic level (T8–12) contributed more to the RoM than the upper (T1–4) and middle (T4–8) levels during flexion and lateral bending. During axial rotation and extension, the middle level (T4–8) contributed the most. Coupled motion was evident, mostly during lateral bending and axial rotation. With aging, the thoracic kyphosis increased by about 3° per decade, whereas the RoM decreased by about 5° per decade for all load directions. These changes with aging mainly occurred in the lower region (T6–12). The influence of sex on thoracic kyphosis and the RoM has been described as partly contradictory. Obesity was found to decrease the thoracic RoM. Studies comparing standing, sitting and lying reported the effect of posture as significant.     

Molecular and Synaptic Bases of CDKL5 Disorder

The X‐linked gene cyclin‐dependent kinase‐like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early‐onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC‐derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis, and synapse formation. The role of CDKL5 in maintaining synaptic function in the mature brain has also begun to emerge. Moreover, mouse models that are deficient for CDKL5 recapitulate some of the key clinical phenotypes in human patients. Here we review these findings related to the function of CDKL5 in the brain and discuss the underlying molecular and cellular mechanisms.     

Fine‐scale patterns of genetic divergence within and between morphologically variable subspecies of the sea urchin Heliocidaris erythrogramma (Echinometridae)

The spatial scale over which genetic divergences occur between populations and the extent that they are paralleled by morphological differences can vary greatly among marine species. In the present study, we use a hierarchical spatial design to investigate genetic structure in Heliocidaris erythrogramma occurring on near shore limestone reefs in Western Australia. These reefs are inhabited by two distinct subspecies: the thick‐spined Heliocidaris erythrogramma armigera and the thin‐spined Heliocidaris erythrogramma erythrogramma, each of which also have distinct colour patterns. In addition to pronounced morphological variation, H. erythrogramma exhibits a relatively short (3–4 days) planktonic phase before settlement and metamorphosis, which limits their capacity for dispersal. We used microsatellite markers to determine whether patterns of genetic structure were influenced more by morphological or life history limitations to dispersal. Both individual and population‐level analyses found significant genetic differentiation between subspecies, which was independent of geographical distance. Genetic diversity was considerably lower within H. e. erythrogramma than within H. e. armigera and genetic divergence was four‐fold greater between subspecies than among populations within subspecies. This pattern was consistent even at fine spatial scales (< 5 km). We did detect some evidence of gene flow between the subspecies; however, it appears to be highly restricted. Within subspecies, genetic structure was more clearly driven by dispersal capacity, although weak patterns of isolation‐by‐distance suggest that there may be other factors limiting gene exchange between populations. Our results show that spatial patterns of genetic structure in Western Australian H. erythrogramma is influenced by a range of factors but is primarily correlated with the distribution of morphologically distinct subspecies. This suggests the presence of reproductive barriers to gene exchange between them and demonstrates that morphological variation can be a good predictor of genetic divergence. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 103 , 578–592.