Allan J. Canty

Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity

The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB1Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB1R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB1Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

The van der Waals Radius of Mercury

Structural studies of mercury compounds are evaluated to providing definite evidence that the van der Waals radius of mercury is in the range 1.7-2.0 A. A general value for the radius should lie at the conservative end of the range, hence 1.73 A, conveniently corresponding to Grdenic’s largely neglected upper limit for any form of bonding, is proposed.

Organopalladium and platinum chemistry in oxidising milieu as models for organic synthesis involving the higher oxidation states of palladium.

This perspective focuses on the higher oxidation state (III, IV) organometallic chemistry of palladium involving a range of strong oxidants, with consideration of platinum chemistry where it is informative for the evaluation of structure and mechanism. Particular emphasis is placed on hypervalent iodine reagents, halogens and related oxidants of intense current interest in organic synthesis, together with linkages in concepts between this chemistry and recent advances in studies of diaryl disulfides, diaryl diselenides, and diaryl peroxides as oxidants.

Cu-Catalyzed Fluorination of Diaryliodonium Salts with KF

A mild Cu-catalyzed nucleophilic fluorination of unsymmetrical diaryliodonium salts with KF is described. This protocol preferentially fluorinates the smaller aromatic ligand on iodine(III). The reaction exhibits a broad substrate scope and proceeds with high chemoselectivity and functional group tolerance. DFT calculations implicate a Cu(I)/Cu(III) catalytic cycle.

The oxidative addition of lodomethane to [PdMe2(bpy)] and the X-ray structure of the organopalladium(IV) product fac-[PdMe3(bpy)l](bpy = 2,2′-bipyridyl)

Oxidative addition of iodomethane to dimethyl(2,2′-bipyridyl)palladium(II) in acetone has resulted in isolation of the first hydrocarbylpalladium(IV) complex, fac-trimethyl(2,2′-bipyridyl)iodopalladium(IV); the complex has been structurally characterized, and reductively eliminates ethane in solution to form methyl(2,2′-bipyridyl)idodpalladium(II).

The DIADEM Data Sets: Representative Light Microscopy Images of Neuronal Morphology to Advance Automation of Digital Reconstructions

The comprehensive characterization of neuronal morphology requires tracing extensive axonal and dendritic arbors imaged with light microscopy into digital reconstructions. Considerable effort is ongoing to automate this greatly labor-intensive and currently rate-determining process. Experimental data in the form of manually traced digital reconstructions and corresponding image stacks play a vital role in developing increasingly more powerful reconstruction algorithms. The DIADEM challenge (short for DIgital reconstruction of Axonal and DEndritic Morphology) successfully stimulated progress in this area by utilizing six data set collections from different animal species, brain regions, neuron types, and visualization methods. The original research projects that provided these data are representative of the diverse scientific questions addressed in this field. At the same time, these data provide a benchmark for the types of demands automated software must meet to achieve the quality of manual reconstructions while minimizing human involvement. The DIADEM data underwent extensive curation, including quality control, metadata annotation, and format standardization, to focus the challenge on the most substantial technical obstacles. This data set package is now freely released (http://diademchallenge.org) to train, test, and aid development of automated reconstruction algorithms.

Organometallic Chemistry of Palladium and Platinum with Poly(pyrazol-1-yl)alkanes and Poly(pyrazol-1-yl)borates

Publisher Summary This chapter covers two new areas of poly(pyrazol-1-yl)alkane chemistry—namely, organopalladium and organoplatinum chemistry and includes their comparisons. Palladium and platinum were involved in the early exploration of poly(pyrazo1-1-y1)borates and poly(pyrazo1-1-y1)alkanes as ligands, and these ligands have subsequently played key roles in the development of organopalladium and platinum chemistry. For example, among the more recent reports is account of allylpalladium chemistry directly related to the initial applications of these ligands. In addition to poly(pyrazol-1-yl)alkanes and -berates, closely related polydentate ligands containing at least one pyrazol-1-yl (pz) group are included, in particular, ligands containing the pyridin-2-yl (py) and N-methylimidazol-2-yl (mim) groups. The poly(pyrazol-1-yl)alkane ligands have been important in the development of the organometallic chemistry of palladium and platinum and recent new applications have included their role in stabilizing hydrocarbylpalladium(1V) compounds and in the synthesis of intramolecular coordination systems, containing tripodal ligands coordinated to platinum(1V).

Alterations in neurofilaments associated with reactive brain changes and axonal sprouting following acute physical injury to the rat neocortex

In order to study the changes in axons related to acute localized physical trauma, a 25 gauge needle was inserted into the somatosensory cortex of anaesthetized adult rats. Animals were examined over 11 time points, from 30 min to 14 days postinjury. Initially, the central needle tract was surrounded by ‘reactive’ abnormal axons characterized by their bulb‐ or ring‐like immunoreactivity for neurofila ments. Quantification demonstrated that these structures reached a peak density at 24 h postinjury, followed by a gradual decrease over 2 weeks. By 5 days postinjury, long axons showing high levels of neurofilament labelling were localized to the lesion area, either aligned parallel to the tract edges or extending into the bridge of tissue forming between the tract edges. Double‐labelling demonstrated a close association between sprouting axons and ferritin‐labelled microglia. Immunolabelling for GAP43 also demonstrated the presence of sprouting axons within this tissue bridge. Ultrastuctural examination showed that sprouting axons contained a high density of neurofilaments, with a leading edge lacking these filaments. Injury to the adult neocortex is associated with reactive and sprouting changes within axons, coordinated with the proliferation of microglia and wound healing. These data also support a role for neurofilaments in axonal sprouting following brain injury.

Molecular mechanisms of axon guidance in the developing corticospinal tract

The great repertoire of movements in higher order mammals comes courtesy of the corticospinal tract (CST) which is able to initiate precise movement of the entire musculature of the axial and limb muscle groups. It forms the longest axonal trajectory in the mammalian central nervous system and its axons must navigate the entire length of the central nervous system--from its origins in the deeper layers of the cerebral cortex down through the cerebral peduncles and brainstem and along the entire length of the spinal cord. This period of navigation is incredibly complex, and relies upon the coordinated regulation of a collection of molecular guidance cues - coming from all of the known major families of guidance cues - the ephrins, slits, Netrins and Semaphorins - that work together to steer the growing axonal tips through the brain and spinal cord. As such a long tract, the CST forms an excellent experimental model to investigate the nature of molecular cues that sequentially guide axons through the central nervous system. Using the rodent as a model system, this review discusses each step of axonal guidance through the major brain regions--starting from the decision to grow ventrally out of the cortical plate to the eventual activity-dependent refinement of circuitry in the spinal grey matter. In recent years, the identification of these guidance cues and their proposed mode of action is beginning to give us a picture at a molecular level of how the CST is guided so accurately over such a long distance.

The synthesis of tripodal nitrogen donor ligands and their characterization as PdIIMe2 and PdIIIMe derivatives

New tripod ligands containing pyridin-2-yl (py), N-methylimidazol-2-yl (mim), and pyrazol-l-y1 (pz) groups have been made by addition of 2-bromopyridine to deprotonated (py)(mim)CH2 or (mim)2CH2 to form (py)2(mim)CH and (py)(mim)2CH, or by simple condensation reactions of (pz)2CO with (mim)CHO or (py)CHO to form (pz)2(mim)CH and (pz)2(py)CH. The ligands may have general application in coordination and organometallic chemistry, especially bis(pyrazol-lyl)(pyridin-2-yl)methane [(pz)2(py)CH], which can be readily synthesized and is an unsymmetrical tripod closely related to (pz)3CH and (py)3CH. Dimethylpalladium( II) and methyl(iodo)palladium(II) complexes of the ligands have been isolated, and compared with complexes of (pz)3CH, (py)3CH, and (pz)4C.