Excess Neuronal Branching Allows for Local Innervation of Specific Dendritic Compartments in Mature Cortex.

The connectivity of cortical microcircuits is a major determinant of brain function; defining how activity propagates between different cell types is key to scaling our understanding of individual neuronal behavior to encompass functional networks. Furthermore, the integration of synaptic currents within a dendrite depends on the spatial organization of inputs, both excitatory and inhibitory. We identify a simple equation to estimate the number of potential anatomical contacts between neurons; finding a linear increase in potential connectivity with cable length and maximum spine length, and a decrease with overlapping volume. This enables us to predict the mean number of candidate synapses for reconstructed cells, including those realistically arranged. We identify an excess of potential local connections in mature cortical data, with densities of neurite higher than is necessary to reliably ensure the possible implementation of any given axo-dendritic connection. We show that the number of local potential contacts allows specific innervation of distinct dendritic compartments.

Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymal-independent mechanisms.

During mammalian lung development, the morphological transition from respiratory tree branching morphogenesis to a predominantly saccular architecture, capable of air-breathing at birth, is dependent on physical forces as well as molecular signaling by a range of transcription factors including the cAMP response element binding protein 1 (Creb1). Creb1(-/-) mutant mice exhibit complete neonatal lethality consistent with a lack of lung maturation beyond the branching phase. To further define its role in the developing mouse lung, we deleted Creb1 separately in the respiratory epithelium and mesenchyme. Surprisingly, we found no evidence of a morphological lung defect nor compromised neonatal survival in either conditional Creb1 mutant. Interestingly however, loss of mesenchymal Creb1 on a genetic background lacking the related Crem protein showed normal lung development but poor neonatal survival. To investigate the underlying requirement for Creb1 for normal lung development, Creb1(-/-) mice were re-examined for defects in both respiratory muscles and glucocorticoid hormone signaling, which are also required for late stage lung maturation. However, these systems appeared normal in Creb1(-/-) mice. Together our results suggest that the requirement of Creb1 for normal mammalian lung morphogenesis is not dependent upon its expression in lung epithelium or mesenchyme, nor its role in musculoskeletal development.

The Effect of Surgery, Injury, and Prolonged Bed Rest on Calf Blood Flow.

Using strain gauge plethysmography, the resting calf blood flow, mainly a measure of muscle blood flow, has been estimated in control subjects, in patients during and after surgical procedures, and in patients during prolonged bed rest following surgery or operation. During general surgical procedures, the calf blood flow was reduced by 38% of the preoperative values. After operation, there was a progressive fall in calf blood flow, the lowest values showing a reduction averaging 58% of the preoperative flow. The reductions in blood flow were associated with an increase in peripheral resistance, indicating that local vasoconstriction was the cause of the reduced flow. Low calf blood flow was also shown to occur in patients who were confined to bed for long periods after injury or operation. It is suggested that by reducing venous return, the decreased calf blood flow during and after surgery, and during prolonged bed rest, may be a factor in the development of deep vein thrombosis in. surgical patients.