Juxtacellular Labeling of Stellate, Disk and Basket Neurons in the Central Nucleus of the Guinea Pig Inferior Colliculus

We reconstructed the intrinsic axons of 32 neurons in the guinea pig inferior colliculus (IC) following juxtacellular labeling. Biocytin was injected into cells in vivo, after first analyzing physiological response properties. Based on axonal morphology there were two classes of neuron: (1) laminar cells (14/32, 44%) with an intrinsic axon and flattened dendrites confined to a single fibrodendritic lamina and (2) translaminar cells (18/32, 56%) with axons that terminated in two or more laminae in the central nucleus (ICc) or the surrounding cortex. There was also one small, low-frequency cell with bushy-like dendrites that was very sensitive to interaural timing differences. The translaminar cells were subdivided into three groups of cells with: (a) stellate dendrites that crossed at least two laminae (8/32, 25%); (b) flattened dendrites confined to one lamina and that had mainly en passant axonal swellings (7/32, 22%) and (c) short, flattened dendrites and axons with distinctive clusters of large terminal boutons in the ICc (3/32, 9%). These terminal clusters were similar to those of cortical basket cells. The 14 laminar cells all had sustained responses apart from one offset response. Almost half the non-basket type translaminar cells (7/15) had onset responses while the others had sustained responses. The basket cells were the only ones to have short-latency (7–9 ms), chopper responses and this distinctive temporal response should allow them to be studied in more detail in future. This is the first description of basket cells in the auditory brainstem, but more work is required to confirm their neurotransmitter and precise post-synaptic targets.

Von Economo Neurons – Primate-Specific or Commonplace in the Mammalian Brain?

The pioneering work by von Economo in 1925 on the cytoarchitectonics of the cerebral cortex revealed a specialized and unique cell type in the adult human fronto-insular (FI) and anterior cingulate cortex (ACC). In modern studies, these neurons are termed von Economo neurons (VENs). In his work, von Economo described them as stick, rod or corkscrew cells because of their extremely elongated and relatively thin cell body clearly distinguishable from common oval or spindle-shaped infragranular principal neurons. Before von Economo, in 1899 Cajal depicted the unique somato-dendritic morphology of such cells with extremely elongated soma in the FI. However, although VENs are increasingly investigated, Cajal’s observation is still mainly being neglected. On Golgi staining in humans, VENs have a thick and long basal trunk with horizontally oriented terminal branching (basilar skirt) from where the axon arises. They are clearly distinguishable from a spectrum of modified pyramidal neurons found in infragranular layers, including oval or spindle-shaped principal neurons. Spindle-shaped cells with highly elongated cell body were also observed in the ACC of great apes, but despite similarities in soma shape, their dendritic and axonal morphology has still not been described in sufficient detail. Studies identifying VENs in non-human species are predominantly done on Nissl or anti-NeuN staining. In most of these studies, the dendritic and axonal morphology of the analyzed cells was not demonstrated and many of the cells found on Nissl or anti-NeuN staining had a cell body shape characteristic for common oval or spindle-shaped cells. Here we present an extensive literature overview on VENs, which demonstrates that human VENs are specialized elongated principal cells with unique somato-dendritic morphology found abundantly in the FI and ACC of the human brain. More research is needed to properly evaluate the presence of such specialized cells in other primates and non-primate species.

Excitable axonal domains adapt to sensory deprivation in the olfactory system

The axon initial segment, nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the faithful, coordinated transmission of action potentials to downstream brain regions. In the olfactory bulb, olfactory discrimination tasks lead to adaptive changes in cell firing patterns, and the output signals must reliably travel large distances to other brain regions along highly myelinated tracts. Whether myelinated axons adapt to facilitate olfactory sensory processing is unknown. Here, we investigate the morphology and physiology of mitral cell axons in the adult olfactory system, and show that unilateral sensory deprivation causes system-wide adaptations in axons. Mitral cell spiking patterns and action potentials also adapted to sensory deprivation. Strikingly, both axonal morphology and mitral cell physiology were altered on both the deprived and non-deprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system.

The variability of MR axon radii estimates in the human brain

The noninvasive quantification of axonal morphology provides an exciting avenue to gain understanding of the function and structure of the central nervous system. Accurate non-invasive mapping of micron-sized axon radii using commonly applied neuroimaging techniques, i.e., diffusion-weighted MRI, has been bolstered by recent hardware developments. In this work, we present the whole brain characterization of the effective MR axon radius and evaluate the inter- and intra-scanner test-retest repeatability and reproducibility to promote the further development of the effective MR axon radius as a neuroimaging biomarker. We observe a coefficient-of-variability of approximately 10% in the voxelwise estimation of the effective MR radius in the test-retest analysis, but demonstrate that the performance can be improved fourfold using a customized along-tract analyses.

In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome

22q11.2 Deletion Syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia, autism, and attention deficit hyperactivity disorder, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterisation of white matter microstructure in both typically-developing children and children with 22q11.2DS using a dedicated magnetic resonance imaging scanner which is sensitive to axonal morphology. By extracting a rich array of diffusion metrics, we present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences between typically-developing and 22q11.2DS children. A recent, large-scale consortium study identified higher diffusion anisotropy and reduced overall mobility of water as hallmark microstructural alterations of white matter in 22q11.2DS, in particular for commissural fibers. We observed similar findings across all white matter tracts in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that microstructural connectivity in 22q11.2DS is mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo mechanistic features of 22q11.2DS, and promote further investigation of shared features in neurodevelopmental and psychiatric disorders.

Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex

GABAergic fast-spiking parvalbumin-positive (PV) interneurons are frequently myelinated in the cerebral cortex. However, the factors governing the topography of cortical interneuron myelination remain incompletely understood. Here, we report that segmental myelination along neocortical interneuron axons is strongly predicted by the joint combination of interbranch distance and local axon caliber. Enlargement of PV+ interneurons increased axonal myelination, while reduced cell size led to decreased myelination. Next, we considered regular-spiking SOM+ cells, which normally have relatively shorter interbranch distances and thinner axon diameters than PV+ cells, and are rarely myelinated. Consistent with the importance of axonal morphology for guiding interneuron myelination, enlargement of SOM+ cell size dramatically increased the frequency of myelinated axonal segments. Lastly, we confirm that these findings also extend to human neocortex by quantifying interneuron axonal myelination from ex vivo surgical tissue. Together, these findings establish a predictive model of neocortical GABAergic interneuron myelination determined by local axonal morphology.