A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

The topology of connections between rat prefrontal and temporal cortices

Understanding the structural organization of the prefrontal cortex (PFC) is an important step toward determining its functional organization. Here we investigated the organization of PFC using different neuronal tracers. We injected retrograde (Fluoro-Gold, 100 nl) and anterograde [Biotinylated dextran amine (BDA) or Fluoro-Ruby, 100 nl] tracers into sites within PFC subdivisions (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) along a coronal axis within PFC. At each injection site one injection was made of the anterograde tracer and one injection was made of the retrograde tracer. The projection locations of retrogradely labeled neurons and anterogradely labeled axon terminals were then analyzed in the temporal cortex: area Te, entorhinal and perirhinal cortex. We found evidence for an ordering of both the anterograde (anterior-posterior, dorsal-ventral, and medial-lateral axes: p < 0.001) and retrograde (anterior-posterior, dorsal-ventral, and medial-lateral axes: p < 0.001) connections of PFC. We observed that anterograde and retrograde labeling in ipsilateral temporal cortex (i.e., PFC inputs and outputs) often occurred reciprocally (i.e., the same brain region, such as area 35d in perirhinal cortex, contained anterograde and retrograde labeling). However, often the same specific columnar temporal cortex regions contained only either labeling of retrograde or anterograde tracer, indicating that PFC inputs and outputs are frequently non-matched

Effective crustal permeability controls fault evolution: An integrated structural, mineralogical and isotopic study in granitic gneiss, Monte Rosa, Northern Italy

Two dextral faults within granitic gneiss in the Monte Rosa nappe, northern Italy reveal key differences in their evolution controlled by evolving permeability and water/rock reactions. The comparison reveals that identical host rock lithologies develop radically different mineralogies within the fault zones, resulting in fundamentally different deformation histories. Oxygen and hydrogen isotope analyses coupled to microstructural characterisation show that infiltration of meteoric water occurred into both fault zones. The smaller Virgin Fault shows evidence of periodic closed system behaviour, which promoted the growth of hydrothermal K-feldspar, whilst the more open system behaviour of the adjacent Ciao Ciao Fault generated a weaker muscovite-rich fault core, which promoted a step change in fault evolution. Effective crustal permeability is a vital control on fault evolution and, coupled to the temperature (i.e. depth) at which key mineral transformations occur, is probably a more significant factor than host rock strength in controlling fault development. The study suggests that whether a fault in granitic basement grows into a large structure may be largely controlled by the initial hydrological properties of the host rocks. Small faults exposed at the surface may therefore be evolutionary “dead-ends” that typically do not represent the early stages in the development of larger faults

Advances in procedural techniques--antegrade.

There have been many technological advances in antegrade CTO PCI, but perhaps most importantly has been the evolution of the "hybrid' approach where ideally there exists a seamless interplay of antegrade wiring, antegrade dissection re-entry and retrograde approaches as dictated by procedural factors. Antegrade wire escalation with intimal tracking remains the preferred initial strategy in short CTOs without proximal cap ambiguity. More complex CTOs, however, usually require either a retrograde or an antegrade dissection re-entry approach, or both. Antegrade dissection re-entry is well suited to long occlusions where there is a healthy distal vessel and limited "interventional" collaterals. Early use of a dissection re-entry strategy will increase success rates, reduce complications, and minimise radiation exposure, contrast use as well as procedural times. Antegrade dissection can be achieved with a knuckle wire technique or the CrossBoss catheter whilst re-entry will be achieved in the most reproducible and reliable fashion by the Stingray balloon/wire. It should be avoided where there is potential for loss of large side branches. It remains to be seen whether use of newer dissection re-entry strategies will be associated with lower restenosis rates compared with the more uncontrolled subintimal tracking strategies such as STAR and whether stent insertion in the subintimal space is associated with higher rates of late stent malapposition and stent thrombosis. It is to be hoped that the algorithms, which have been developed to guide CTO operators, allow for a better transfer of knowledge and skills to increase uptake and acceptance of CTO PCI as a whole

Refined architecture of the WASP-8 system: a cautionary tale for traditional Rossiter-McLaughlin analysis

Probing the trajectory of a transiting planet across the disk of its star through the analysis of its Rossiter-McLaughlin effect can be used to measure the differential rotation of the host star and the true obliquity of the system. Highly misaligned systems could be particularly conducive to these mesurements, which is why we reanalysed the HARPS transit spectra of WASP-8b using the 'Rossiter-McLaughlin effect reloaded' (reloaded RM) technique. This approach allows us to isolate the local stellar CCF emitted by the planet-occulted regions. As a result we identified a $\sim$35% variation in the local CCF contrast along the transit chord, which might trace a deepening of the stellar lines from the equator to the poles. Whatever its origin, such an effect cannot be detected when analyzing the RV centroids of the disk-integrated CCFs through a traditional velocimetric analysis of the RM effect. Consequently it injected a significant bias into the results obtained by Queloz et al. (2010) for the projected rotational velocity $v_{eq} \sin i_{\star}$ (1.59$\stackrel{+0.08}{_{-0.09}}$ km/s) and the sky-projected obliquity $\lambda$ (-123.0$\stackrel{+3.4}{_{-4.4}}^{\circ}$). Using our technique, we measured these values to be $v_{eq} \sin i_{\star}$ = 1.90$\pm$0.05 km/s and $\lambda$ = -143.0$\stackrel{+1.6}{_{-1.5}}^{\circ}$. We found no compelling evidence for differential rotation of the star, although there are hints that WASP-8 is pointing away from us with the stellar poles rotating about 25% slower than the equator. Measurements at higher accuracy during ingress/egress will be required to confirm this result. In contrast to the traditional analysis of the RM effect, the reloaded RM technique directly extracts the local stellar CCFs, allowing us to analyze their shape and to measure their RV centroids, unbiased by variations in their contrast or FWHM.Comment: Accepted for publication in A&A. 12 page

Birth of a Learning Law

Defense Advanced Research Projects Agency; Office of Naval Research (N00014-95-1-0409, N00014-95-1-0657, N00014-92-J-1309