The exit of axons and glial membrane from the developing Drosophila retina requires integrins

Coordinated development of neurons and glia is essential for the establishment of neuronal circuits during embryonic development. In the developing Drosophila visual system, photoreceptor (R cell) axons and wrapping glial (WG) membrane extend from the eye disc through the optic stalk into the optic lobe. Extensive studies have identified a number of genes that control the establishment of R-cell axonal projection pattern in the optic lobe. The molecular mechanisms directing the exit of R-cell axons and WG membrane from the eye disc, however, remain unknown. In this study, we show that integrins are required in R cells for the extension of R-cell axons and WG membrane from the eye disc into the optic stalk. Knockdown of integrins in R cells but not WG caused the stalling of both R-cell axons and WG membrane in the eye disc. Interfering with the function of Rhea (i.e. the Drosophila ortholog of vertebrate talin and a key player of integrin-mediated adhesion), caused an identical stalling phenotype. These results support a key role for integrins on R-cell axons in directing R-cell axons and WG membrane to exit the eye disc.

NEURONAL-GLIAL MEMBRANE CONTACTS DURING PESSIMAL ELECTRICAL STIMULATION

After the creation of a method for obtaining inter-neuronal gap junctions in a nervous system devoid of glia, it is expedient to reproduce gap neuronal-glial contacts on a model that also contains hybrid neuronal-glial gap junctions, which, as you know, are functionally fundamentally different from inter-neuronal contacts. The experiments were carried out on the truncus sympathicus ganglia of laboratory rats using pessimal electrical stimulation and transmission electron microscopy. Electrical activation of ganglia with a frequency of up to 100 Hz revealed local and widespread variants of various neuronal-glial connections (contacts, bridges), fringed with peri-membrane filamentous proteins. They had a blurred veil that masked two-layer neuro-membranes. Some of the contacts resembled slit or dense 5-layer structures without a visible inter-neuronal slit, but with an extreme decrease in the thickness of the contact slit. The main result of the experiments was the formation, in addition to slotted, multiple septate (ladder) contacts. Relatively independent aggregates of the electron-dense substance of the septa were located inside the intercellular gaps, crossing both adjacent membranes, and, possibly, permeate of them. Near-membrane, poorly outlined pyramid-like protein cones associated with both cell membranes were also formed. Such membranes appeared to be dotted-dashed, that is, not continuous. A significant number of septic contact membranes had endocytic invaginations (invaginations) facing neuroplasm with pyramid-like marginal projections. All reactive altered structures that have arisen de novo are considered by the authors as developed under the influence of frequency electrical stimulation of denaturation and aggregation of intrinsic and perimembrane proteins.

The Pebble/Rho1/Anillin pathway controls polyploidization and axonal wrapping activity in the glial cells of the Drosophila eye

During development glial cell are crucially important for the establishment of neuronal networks. Proliferation and migration of glial cells can be modulated by neurons, and in turn glial cells can differentiate to assume key roles such as axonal wrapping and targeting. To explore the roles of actin cytoskeletal rearrangements in glial cells, we studied the function of Rho1 in Drosophila developing visual system. We show that the Pebble (RhoGEF)/Rho1/Anillin pathway is required for glia proliferation and to prevent the formation of large polyploid perineurial glial cells, which can still migrate into the eye disc if generated. Surprisingly, this Rho1 pathway is not necessary to establish the total glial membrane area or for the differentiation of the polyploid perineurial cells. The resulting polyploid wrapping glial cells are able to initiate wrapping of axons in the basal eye disc, however the arrangement and density of glia nuclei and membrane processes in the optic stalk are altered and the ensheathing of the photoreceptor axonal fascicles is reduced.

MORPHOLOGICAL STUDY OF COMMUNICATION BETWEEN THE LONGITUDINAL STRIPS AND THE HUMAN CORPUS CALLOSUM

Background. It is established that there is an anatomical relationship between the corpus callosum and longitudinal strips. These formations must correlate to the common commissural system of the corpus callosum conductors. At present this issue in such a formulation is not considered in literature on Neuromorphology.Objective. The study was aimed to determine the commutations between the longitudinal strips and commissural conductors of the corpus callosum.Methods. The corpus callosum of people aged from 36 to 60 was studied. Some slices of the corpus callosum stem were used for impregnation and then inserted in paraffin blocks. Another part of these slices was subjected to plastination in epoxy resin.Results. Lateral longitudinal strips contain significantly greater mass of nerve conductors. Most of them compactly pass along limbic ring, while the other part is combined to nerve fibres of the corpus callosum commissural cords. The longitudinal strips are coated with an outer limiting glial membrane (grey coating).Conclusions. By means of the corpus callosum the connections between conscious and subconscious brain areas are structurally fixed. It can be assumed that longitudinal strips have relation to hippocampal area, related to the ancient formation of the pallium. This does not exclude the fact that the nerve fibres, found within longitudinal strips may have projections on the cortical cells of vaulted gyrus, which is considered to be paleopallium sphere. So, this interaction between the ancient and the old cortex should presumably be carried out by means of lateral longitudinal strips.

Facilitation of Neuronal Responses by Intrinsic Default Mode Network Activity

Default mode network (DMN) shows intrinsic, high-level activity at rest. We tested a hypothesis proposed for its role in sensory information processing: Intrinsic DMN activity facilitates neural responses to sensory input. A neural network model, consisting of a sensory network (Nsen) and a DMN, was simulated. The Nsen contained cell assemblies. Each cell assembly comprised principal cells, GABAergic interneurons (Ia, Ib), and glial cells. We let the Nsen carry out a perceptual task: detection of sensory stimuli. During DMN activation, glial cells were hyperpolarized by Ia-to-glia circuitry, by which glial membrane transporters imported GABA molecules from the extracellular space and decreased ambient GABA concentration. Acting on extrasynaptic GABA receptors, the decrease in ambient GABA concentration reduced inhibitory current in a tonic manner. This depolarized principal cells below their firing threshold during the ongoing spontaneous time period and accelerated their reaction speed to a sensory stimulus. During the stimulus presentation period, the Nsen inhibited the DMN and caused DMN deactivation. The DMN deactivation made Nsen Ia cells cease firing, thereby stopping the glial membrane hyperpolarization, quitting the GABA import, returning to the basal ambient GABA level, and thus enhancing global inhibition. Notably, the stimulus-relevant P cell firing could be maintained when GABAergic gliotransmission via Ia-glia signaling worked, decreasing ambient GABA concentration around the stimulus-relevant P cells. This enabled the Nsen to reliably detect the stimulus. We suggest that intrinsic default model network activity may accelerate the reaction speed of the sensory network by modulating its ongoing-spontaneous activity in a subthreshold manner. Ambient GABA contributes to achieve an optimal ongoing spontaneous subthreshold neuronal state, in which GABAergic gliotransmission triggered by the intrinsic default model network activity may play an important role.

The Indusium Griseum

BACKGROUND: Although the indusium griseum (IG) is often seen by the neurosurgeon, almost nothing exists in the literature regarding its anatomic structure. Some have postulated that this structure is a remnant of the hippocampus, and some have found memory deficits in patients after callosotomy. OBJECTIVE: To further investigate the anatomy of the IG in humans through gross and histological analysis. METHODS: The IG from 10 adult cadaveric brains underwent microdissection and immunohistochemical analysis. RESULTS: Grossly, the IG was on average 2 cm in width over the body and genu of the corpus callosum (CC) and traveled in intimate contact anteriorly over the lamina terminalis, and posteriorly it was adherent to the splenium of the CC. Histologically, the IG is a thin layer of hypocellular glial tissue interposed between the pia and the CC. Glial cells composed the cellular constituents of the IG, and compared with the underlying CC, the IG was hypomyelinated. The fibers/axons of the IG travel in a perpendicular plane compared with those of the CC, and the IG varied in thickness from one area to the other and was occasionally discontinuous. CONCLUSION: The IG is a glial membrane with no neuronal content or obvious connections to the hippocampus. Based on this study, transection of this membrane with callosotomy should not be the reason for postoperative memory loss seen in some of these patients. Future studies aimed at elucidating the function of the IG in humans are now warranted.

Myosin II has distinct functions in PNS and CNS myelin sheath formation

The myelin sheath forms by the spiral wrapping of a glial membrane around the axon. The mechanisms responsible for this process are unknown but are likely to involve coordinated changes in the glial cell cytoskeleton. We have found that inhibition of myosin II, a key regulator of actin cytoskeleton dynamics, has remarkably opposite effects on myelin formation by Schwann cells (SC) and oligodendrocytes (OL). Myosin II is necessary for initial interactions between SC and axons, and its inhibition or down-regulation impairs their ability to segregate axons and elongate along them, preventing the formation of a 1:1 relationship, which is critical for peripheral nervous system myelination. In contrast, OL branching, differentiation, and myelin formation are potentiated by inhibition of myosin II. Thus, by controlling the spatial and localized activation of actin polymerization, myosin II regulates SC polarization and OL branching, and by extension their ability to form myelin. Our data indicate that the mechanisms regulating myelination in the peripheral and central nervous systems are distinct.