Anillin promotes astral microtubule-directed cortical myosin polarization

Assembly of a cytokinetic contractile ring is a form of cell polarization in which the equatorial cell cortex becomes differentiated from the polar regions. Microtubules direct cytokinetic polarization via the central spindle and astral microtubules. The mechanism of central spindle-directed furrow formation is reasonably well understood, but the aster-directed pathway is not. In aster-directed furrowing, cytoskeletal factors accumulate to high levels at sites distal to the asters and at reduced levels at cortical sites near the asters. In this paper, we demonstrate that the cytoskeletal organizing protein anillin (ANI-1) promotes the formation of an aster-directed furrow in Caenorhabditis elegans embryos. Microtubule-directed nonmuscle myosin II polarization is aberrant in embryos depleted of ANI-1. In contrast, microtubule-directed polarized ANI-1 localization is largely unaffected by myosin II depletion. Consistent with a role in the induction of cortical asymmetry, ANI-1 also contributes to the polarization of arrested oocytes. Anillin has an evolutionarily conserved capacity to associate with microtubules, possibly providing an inhibitory mechanism to promote polarization of the cell cortex.     

The role of calcium in monoamine-induced depression of cerebral cortical neurones

The calcium antagonists, lanthanum, verapamil and manganese, have been shown to antagonize the depressant actions of ionto-phoretically applied monoamines (noradrenaline, 5-hydroxytryptamine, dopamine and histamine), but not of γ-aminobutyric acid, on cerebral cortical neurones. Cocaine and ethanol, which also affect membrane calcium fluxes, have a similar antagonistic action. These findings suggest that calcium ions are essential for, and perhaps mediate, the characteristic depressant actions of the monoamines on cerebral cortical neurones.     

Differential mechanisms of glutamate receptor regulation of SynGAP in cortical neurones

One prime candidate linking N-methyl-D-aspartate (NMDA) receptors to the regulation of the MAP kinase cascade is SynGAP, a negative regulator of Ras. In order to assess how a physiological stimulus can alter SynGAP activity, an appropriate whole cell system must be used and SynGAP must be specifically extracted from membranes whilst preserving the catalytic activity of the protein. Here, we have achieved this and studied the effect of NMDA/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptor stimulations on SynGAP activity in cortical neurones. Furthermore, we have examined the role of extracellular Ca2+, CaM kinase II and the PSD-95-NR2B subunit interaction in SynGAP activity regulation and propose a novel convergence of signalling between AMPA, kainate and NMDA receptors.     

Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones

Statins [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors] exert cholesterol-independent pleiotropic effects that include anti-thrombotic, anti-inflammatory, and anti-oxidative properties. Here, we examined direct protective effects of atorvastatin on neurones in different cell damage models in vitro. Primary cortical neurones were pre-treated with atorvastatin and then exposed to (i) glutamate, (ii) oxygen-glucose deprivation or (iii) several apoptosis-inducing compounds. Atorvastatin significantly protected from glutamate-induced excitotoxicity as evidenced by propidium iodide staining, nuclear morphology, release of lactate dehydrogenase, and mitochondrial tetrazolium metabolism, but not from oxygen-glucose deprivation or apoptotic cell death. This anti-excitototoxic effect was evident with 2-4 days pre-treatment but not with daily administration or shorter-term pre-treatment. The protective properties occurred independently of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition because co-treatment with mevalonate or other isoprenoids did not reverse or attenuate neuroprotection. Atorvastatin attenuated the glutamate-induced increase of intracellular calcium, which was associated with a modulation of NMDA receptor function. Taken together, atorvastatin exerts specific anti-excitotoxic effects independent of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition, which has potential therapeutic implications.     

Excitability cycles of epileptic after-discharges in rats

An epileptic seizure is regularly followed by a postictal depression and then by a phase of increased excitability. The time course of these two phases was described for two types of epileptic after-discharges induced by stimulation of the hippocampus and/or the thalamus in acute experiments in rats. Using hippocampal stimulation, an interval of 10 min was necessary for induction of the second self-sustained after-discharge (SSAD) of the same duration as the first one. Significant prolongation of the second SSAD appeared with a 30-min interstimulation interval. The spike-and-wave rhythm induced by stimulation of thalamic nuclei exhibited a shorter refractory phase - up to 5 min - and also the facilitation took place sooner: with 15-min intervals a significant increase in duration of SSAD was recovered. The results are discussed in connection with the kindling model of epilepsy.     

Cell type specificity of local cortical connections

The function of the cerebral cortex is dependent on the precise organization of the circuits formed by its component neurons. The connections between neurons are not random, but are specific at multiple levels of organization. For example, each cortical area connects to only a selected subset of other areas and within any given area the axonal and dendritic arbors of individual neurons arborize in precise, layer-specific patterns (for review see Felleman & Van Essen, 1991; Callaway, 1998) . In each layer there are dendrites from multiple cell types including cells with somata both within and outside that layer. Anatomical studies have shown that axons arborizing in a particular cortical layer can connect selectively onto dendrites of some cell types in the layer, while avoiding the dendrites of other cell types (e.g. Freund & Gulyas, 1991; Hornung & Celio, 1992; Staiger et al., 1996). These cell type specific connections are, however, difficult to elucidate with anatomical methods, so the frequency of such specificity has remained elusive. Recent experimental methods combining intracellular recording of single neurons with focal neuronal stimulation by uncaging glutamate with light (“photostimulation”) have made the analysis of cell type specific cortical connections more tractable. These studies show that cell type specificity of connections is prevalent in cortex. Here I review photostimulation-based studies investigating the laminar sources of cortical input to distinct cell types in the visual and somatosensory cortices of rats and the primary visual cortex of monkeys.     

Neomycin and ruthenium red antagonism of monoaminergic depression of cerebral cortical neurones

Neomycin and ruthenium red, two agents which are known to interfere with the transport and binding of calcium, antagonize the depressant actions of noradrenaline and 5-hydroxytryptamine on cerebral cortical neurones. Ouabain and sodium azide, metabolic inhibitors, also block the action of noradrenaline. These findings support earlier suggestions that monoaminergic depression of cortical neurones involves a calcium-dependent mechanism which may be linked to a membrane ion pump.     

Temporal profile of ultrastructural changes in cortical neurones after a compression lesion

We studied the occurrence of apoptosis and secondary delayed cell death at various time points in the penumbra zone, which is the target for therapeutic intervention after stroke. A compression lesion was induced in the right sensory motor cortex of rat brains. At 0.5, 1, 3, 6, 12, 24, 48 and 72 h after lesioning, motor functions were evaluated by behavioral tests, and cortical layers IV and V were examined by electron microscopy. Behavioral recovery was observed at 48 h after lesioning. At 0.5-1 h in the lesioned area, the neuropil was expanded and contained affected cells. Apoptotic cells were found between 0.5-72 h, and at 12 h, 47.3 % of the total cell number was apoptotic cells. On the contralateral side, cells showed an enlarged endoplasmic reticulum at 3 h, indicating secondary delayed cell death. Our results show that a compression lesion is a useful model for studying ultrastructural changes in injured cells. The lesion results in the penumbra zone with apoptotic cell death between 0.5-72 h. As secondary delayed cell death occurred on the contralateral side at three hours after lesioning might be the time period during which injured, but still viable, neurons can be targets for acute treatment.     

Critical period plasticity in local cortical circuits

Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.     

Effect of interruption of descending cortical connections on unit responses to extracellular polarization in the lateral geniculate body

Acute experiments on cats showed that unilateral division of projection connections from the cerebral cortex gives rise to definite changes in the effects of extracellular polarization of lateral geniculate neurons: in 40% of cells the regular firing pattern is disturbed in the initial period of action of anodal polarization, the number of cells with after-responses and prolonged changes in spontaneous firing pattern is significantly reduced, and the number of neurons capable of modifying their type of activity under the influence of an incoming polarizing current is also reduced. After interruption of the descending cortical connections the functional characteristics of the lateral geniculate neurons are altered, with a resulting narrowing of the range of their physiological responses to the polarizing current. These facts suggest that the most complex processes of tonic regulation of unit activity in the lateral geniculate bodies require the active participation of the cerebral cortex.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 6, pp. 629–635, November-December, 1972.