The mammalian telencephalon, which comprises the cerebral cortex, olfactory bulb, hippocampus, basal ganglia, and amygdala, is the most complex and intricate region of the CNS. It is the seat of all higher brain functions including the storage and retrieval of memories, the integration and processing of sensory and motor information, and the regulation of emotion and drive states. In higher mammals such as humans, the telencephalon also governs our creative impulses, ability to make rational decisions, and plan for the future. Despite its massive complexity, exciting work from a number of groups has begun to unravel the developmental mechanisms for the generation of the diverse neural cell types that form the circuitry of the mature telencephalon. Here, we review our current understanding of four aspects of neural development. We first begin by providing a general overview of the broad developmental mechanisms underlying the generation of neuronal and glial cell diversity in the telencephalon during embryonic development. We then focus on development of the cerebral cortex, the most complex and evolved region of the brain. We review the current state of understanding of progenitor cell diversity within the cortical ventricular zone and then describe how lateral signaling via the Notch‐Delta pathway generates specific aspects of neural cell diversity in cortical progenitor pools. Finally, we review the signaling mechanisms required for development, and response to injury, of a specialized group of cortical stem cells, the radial glia, which act both as precursors and as migratory scaffolds for newly generated neurons.

The ferret has emerged as an important animal model for the study of neocortical development. Although detailed studies of the birthdates of neurons populating the ferret visual cortex are available, the birthdates of neurons that reside in somatosensory cortex have not been determined. The current study used bromodeoxyuridine to establish when neurons inhabiting the somatosensory cortex are generated in the ferret; some animals also received injections of [3H]thymidine. In contrast to reports of neurogenesis in ferret visual cortex, most neurons populating the somatosensory cortex have been generated by birth. Although components of all somatosensory cortical layers have been produced at postnatal day 0, the layers are not distinctly formed but develop over a period of several weeks. A small number of neurons continue to be produced for a few days postnatally. The majority of cells belonging to a given layer are born over a period of approximately 3 days, although the subplate and last (layer 2) generated layer take somewhat longer. Although neurogenesis of the neocortex begins along a similar time line for visual and somatosensory cortex, the neurons populating the visual cortex lag substantially during the generation of layer 4, which takes more than 1 week for ferret visual cortex. Layer formation in ferret somatosensory cortex follows many established principles of cortical neurogenesis, such as the well-known inside-out development of cortical layers and the rostro-to-caudal progression of cell birth. In comparison with the development of ferret visual cortex, however, the generation of the somatosensory cortex occurs remarkably early and may reflect distinct differences in mechanisms of development between the two sensory areas.

PurposeThis study was a systematic evaluation across different and prominent diffusion MRI models to better understand the ways in which scalar metrics are influenced by experimental factors, including experimental design (diffusion‐weighted imaging [DWI] sampling) and noise.MethodsFour diffusion MRI models—diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator MRI (MAP‐MRI), and neurite orientation dispersion and density imaging (NODDI)—were evaluated by comparing maps and histogram values of the scalar metrics generated using DWI datasets obtained in fixed mouse brain with different noise levels and DWI sampling complexity. Additionally, models were fit with different input parameters or constraints to examine the consequences of model fitting procedures.ResultsExperimental factors affected all models and metrics to varying degrees. Model complexity influenced sensitivity to DWI sampling and noise, especially for metrics reporting non‐Gaussian information. DKI metrics were highly susceptible to noise and experimental design. The influence of fixed parameter selection for the NODDI model was found to be considerable, as was the impact of initial tensor fitting in the MAP‐MRI model.ConclusionAcross DTI, DKI, MAP‐MRI, and NODDI, a wide range of dependence on experimental factors was observed that elucidate principles and practical implications for advanced diffusion MRI. Magn Reson Med 78:1767–1780, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

This article provides a review of brain tissue alterations that may be detectable using diffusion MRI (dMRI) approaches and an overview and perspective on the modern dMRI toolkits for characterizing alterations that follow traumatic brain injury (TBI). Non-invasive imaging is a cornerstone of clinical treatment of TBI and has become increasingly used for pre-clinical and basic research studies. In particular, quantitative MRI methods have the potential to distinguish and evaluate the complex collection of neurobiological responses to TBI arising from pathology, neuroprotection and recovery. Diffusion MRI provides unique information about the physical environment in tissue and can be used to probe physiological, architectural and microstructural features. While well-established approaches such as diffusion tensor imaging (DTI) are known to be highly sensitive to changes in the tissue environment, more advanced diffusion MRI techniques have been developed that may offer increased specificity or new information for describing abnormalities. These tools are promising, but incompletely understood in the context of TBI. Furthermore, model dependencies and relative limitations may impact the implementation of these approaches and the interpretation of abnormalities in their metrics. The objective of this paper is to present a basic review and comparison across diffusion MRI methods as they pertain to the detection of the most commonly observed tissue and cellular alterations following TBI.

Although the role of acetylcholine in processing stimuli in the cerebral cortex is becoming defined, the impact of cholinergic activity on the character of cortical maps remadns unclear. In the somatosensory cortex, topographic maps appear capable of lifelong modifications in response to alterations in the periphery. One factor proposed to influence this adaptational ability is the presence of acetylcholine in the cortex. The studies presented here, using the 2-deoxyglucose technique, demonstrate that the unilateral removal of a digit in cats, followed by stimulation of an adjacent digit, produces a pattern of metabolic activity in the somatosensory cortex that is dramatically expanded when compared with the opposite (normal) hemisphere. In contrast, experiments in which the somatosensory cortex was depleted of acetylcholine and the animal received a similar amputation led not to patterns of expanded metabolic activity, but rather to reductions in the evoked metabolic distribution. These studies implicate acetylcholine in normal map formation and in the maintenance of the capacity of cortical maps to adapt to changes in the periphery.Several lines of evidence suggest that the cholinergic projection from the basal forebrain plays an important role in cortical physiology and plasticity. For example, in 1986, Bear and Singer (1) demonstrated that depletion of cortical acetylcholine (ACh) following lesions of the basal forebrain disrupts ocular dominance plasticity in kitten area 17. Interestingly, this effect required the concurrent depletion of cortical norepinephrine. Cortical ACh depletion has also been shown to cause a reduction in the cortical response to sensory stimulation, measured both electrophysiologically (2) and metabolically (3, 4). For example, Sato et al. (2) found that lesions of the basal forebrain, which depleted the visual cortex of ACh, led to neuronal responses in visual cortex that were sluggish and depressed. Previous studies in cat somatosensory cortex found that ACh depletion by basal forebrain lesions, or by the pharmacologic antagonism of ACh through topical applications of atropine, caused the stimulus-evoked metabolic pattern to be reduced in dimension and intensity in the hemisphere ipsilateral to the depletion or application of atropine (3). On the other hand, iontophoretic application of exogenous ACh can augment the responses to peripheral stimulation in visual, somatosensory, and auditory cortex (5-11). In these sensory cortical regions, the pairing of ACh with appropriate stimuli usually enhances cortical responses. In some cases, the augmentation substantially outlasts presentation of the stimulus, causing a long-lasting potentiation of neuronal responsivity (11)(12)(13)(14).In the somatosensory cortex, topographic maps of the body surface appear capable of remodeling and demonstrating plastic changes throughout adulthood. Studies that evaluate the cortical response to various peripheral manipulations in adults show dramatic rearrangements of cortical topographic maps ...