This aim of this study was to assess the discriminatory value of fractal and grey level co-occurrence matrix (GLCM) analysis methods in standard microscopy analysis of two histologically similar brain white mass regions that have different nerve fiber orientation. A total of 160 digital micrographs of thionine-stained rat brain white mass were acquired using a Pro-MicroScan DEM-200 instrument. Eighty micrographs from the anterior corpus callosum and eighty from the anterior cingulum areas of the brain were analyzed. The micrographs were evaluated using the National Institutes of Health ImageJ software and its plugins. For each micrograph, seven parameters were calculated: angular second moment, inverse difference moment, GLCM contrast, GLCM correlation, GLCM variance, fractal dimension, and lacunarity. Using the Receiver operating characteristic analysis, the highest discriminatory value was determined for inverse difference moment (IDM) (area under the receiver operating characteristic (ROC) curve equaled 0.925, and for the criterion IDM≤0.610 the sensitivity and specificity were 82.5 and 87.5%, respectively). Most of the other parameters also showed good sensitivity and specificity. The results indicate that GLCM and fractal analysis methods, when applied together in brain histology analysis, are highly capable of discriminating white mass structures that have different axonal orientation.

In this study we examine the postnatal development of retinogeniculate axons projecting to the magnocellular (M axons), parvocellular (P axons), and koniocellular (K axons) layers of the lateral geniculate nucleus (LGN) in the prosimian primate, Galago crassicaudatus, in order to: (1) understand how individual retinogeniculate axons in primates mature postnatally, and (2) determine whether differences exist in the development of separate classes of axons that are known to be presynaptic to physiologically distinct cells in adults. In galagos, magnocellular, parvocellular, and koniocellular LGN layers contain Y-, X-, and W-like physiological cell classes, respectively (Norton & Casagrande, 1982).

In vitro and in vivo optic tract bulk injections of horseradish peroxidase (HRP) were made in animals ranging in age from the day of birth (P0) to adulthood. Two hundred and fifty axonal arbors were completely reconstructed from serial sections and examined qualitatively for general features of maturity and compared quantitatively for changes in shape, arbor width, area, volume, bouton number, and bouton density.

Our results confirm that in adult galagos M arbors are large and radially symmetric; P arbors are medium sized and elongated perpendicular to layer borders; K arbors are small and generally oriented parallel to layer borders. At birth, M, P, and K arbors, although still distinct and confined to layers, are qualitatively and quantitatively immature. Both the pattern and pace of maturation differ between classes. Overall, M arbors mature before P arbors which in turn mature before K arbors. Within classes, arbors representing central vision appear to develop about a week ahead of those representing peripheral vision; no differences are evident between the development of crossed and uncrossed arbors. In no case do arbors exhibit a period of postnatal exuberance, wherein arbors are larger than those of the adult as reported for cat X retinal axons. However, in width and bouton density P arbors are mature at P0 and thus occupy relatively more space in the nucleus compared to adult. All arbors mature rapidly and appear adult-like by the 4th or 5th postnatal week.

Myelination is necessary both for rapid salutatory conduction and the long-term survival of the axon. In the CNS the myelin sheath is formed by the oligodendrocytes. Each oligodendrocyte myelinates several axons and, as the number of wraps around each axon is determined precisely by the axon diameter, this requires a close, highly regulated interaction between the axons and each of the oligodendrocyte processes. Adhesion molecules are likely to play an important role in the bi-directional signalling between axon and oligodendrocyte that underlies this interaction. Here we review the current knowledge of the function of adhesion molecules in the different phases of oligodendrocyte differentiation and myelination, and discuss how the properties of these proteins defined by other cell biological systems indicates potential roles in oligodendrocytes. We show how the function of a number of different adhesion and cell–cell interaction molecules such as polysialic acid neural cell adhesion molecule, Lingo-1, Notch, neuregulin, integrins and extracellullar matrix proteins provide negative and positive signals that coordinate the formation of the myelin membrane. Compiling this information from a number of different cell biological and genetic experiments helps us to understand the pathology of multiple sclerosis and direct new areas of research that might eventually lead to potential drug targets to increase remyelination.

The A1 cell is an axon-bearing amacrine cell of the primate retina with a diffusely stratified, moderately branched dendritic tree (∼400 μm diameter). Axons arise from proximal dendrites forming a second concentric, larger arborization (>4 mm diameter) of thin processes with bouton-like swellings along their length. A1 cells are ON-OFF transient cells that fire a brief high frequency burst of action potentials in response to light (Stafford & Dacey, 1997). It has been hypothesized that A1 cells receive local input to their dendrites, with action potentials propagating output via the axons across the retina, serving a global inhibitory function. To explore this hypothesis we recorded intracellularly from A1 cells in an in vitro macaque monkey retina preparation. A1 cells have an antagonistic center-surround receptive field structure for the ON and OFF components of the light response. Blocking the ON pathway with L-AP4 eliminated ON center responses but not OFF center responses or ON or OFF surround responses. Blocking GABAergic inhibition with picrotoxin increased response amplitudes without affecting receptive field structure. TTX abolished action potentials, with little effect on the sub-threshold light response or basic receptive field structure. We also used multi-photon laser scanning microscopy to record light-induced calcium transients in morphologically identified dendrites and axons of A1 cells. TTX completely abolished such calcium transients in the axons but not in the dendrites. Together these results support the current model of A1 function, whereby the dendritic tree receives synaptic input that determines the center-surround receptive field; and action potentials arise in the axons, which propagate away from the dendritic field across the retina.

We examined the functional properties of a low-voltage-activated (LVA) calcium current in ganglion cells of the neotenous tiger salamander (Ambystoma tigrinum) retina. Our analysis was based on whole-cell recordings from acutely dissociated ganglion cell bodies identified by retrograde dye injections. Using a continuously perfused cell preparation, the LVA current was isolated with the use of potassium channel blocking agents added to the bathing medium and the pipette solution, while tetrodotoxin was added to the bathing medium to block Na+ channels. Approximately 70% of ganglion cells had an easily identified LVA current. The LVA current activated at membrane potentials more positive than −90 mV, and inactivated rapidly. It was relatively insensitive to nickel (IC50 > 500 μM) and amiloride (IC50 > 750 μM). Voltage- and current-clamp studies allowed us to generate a model of this current using the NEURON simulation program. Studies were also carried out to measure the LVA Ca2+ current in ganglion cells with dendrites to confirm that it had a significant dendritic representation. Physiological mechanisms that may depend on LVA Ca2+ currents are discussed with an emphasis on the role that dendrites play in ganglion cell function.

Interactions between neurons and glial cells are crucial for nervous system development and function in all complex organisms, and many functional, morphological and molecular features of glia are well conserved among species. Here we review studies of the longitudinal glia (LG) in the Drosophila CNS. The LG envelop the neuropil in a membrane sheath, and have features resembling both oligodendrocytes and astrocytes. Because of their unique lineage, morphology and molecular features, the LG provide an excellent model to study the genetic mechanisms underlying glial subtype differentiation and diversity, glial morphogenesis and neuron–glial interactions during development. In addition, they are proving useful in understanding how glial cells maintain ion and neurotransmitter homeostasis and protect neurons from environmental insult.

Minocycline, a tetracycline derivative with pleiotropic biological effects, exhibits anti-inflammatory properties in several models of CNS disease. In addition to reducing production of inflammatory mediators, it has been postulated that minocycline might also be directly neuroprotective under these circumstances. Therefore, we investigated the effect of minocycline on primary cortical neuronal cultures exposed to a nitric oxide (NO)-donor. Cultures were assessed for neuronal survival, axon survival and markers of intracellular signaling pathways. The NO donor significantly increased neuronal death and minocycline was protective under these conditions. Furthermore NO-induced reductions in axonal length were significantly attenuated by minocycline. Improvements in axonal length were dependent on mitogen-activated protein kinase (MAP kinase)/extracellular signal-related kinase (Erk) signaling, whereas phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling was important in neuronal survival. Further investigation into MAP kinase signaling pathways revealed inhibition of p38 MAP kinase and c-jun N-terminal kinase (JNK) signaling by minocycline. JNK pathways were activated by trophic factor-withdrawal and minocycline attenuated neuronal death induced by trophic withdrawal. These results indicate that, in addition to anti-inflammatory properties, minocycline has direct protective effects on neurons and provides further evidence for its use in disorders of the CNS.