Modulation of Coordinated Activity across Cortical Layers by Plasticity of Inhibitory Synapses

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Inverted pyramidal neurons and their axons in the neocortex of reeler mutant mice

Summary Inverted pyramidal neurons are very abundant in the cerebral cortex of the adult reeler mutant mouse. Two types of inverted pyramid are found in rapid Golgi impregnations. In the first type the axon starts from the base of the cell body and bends towards the white matter. In the second type, which is more common, the axon emerges from the apical dendritic tree and descends directly towards the white matter.Despite its abnormal topography, the site of origin of the axon in pyramids of the second type displays a normal differentiation, when analysed with the electron microscopic Golgi technique, suggesting that the ectopic initial axon segment is able to fulfil its normal functions.     

Distinct intracellular signaling mediates C‐MET regulation of dendritic growth and synaptogenesis

Hepatocyte growth factor (HGF) activation of the MET receptor tyrosine kinase influences multiple neurodevelopmental processes. Evidence from human imaging and mouse models shows that, in the forebrain, disruptions in MET signaling alter circuit formation and function. One likely means of modulation is by controlling neuron maturation. Here, we examined the signaling mechanisms through which MET exerts developmental effects in the neocortex. In situ hybridization revealed that hgf is located near MET‐expressing neurons, including deep neocortical layers and periventricular zones. Western blot analyses of neocortical crude membranes demonstrated that HGF‐induced MET autophosphorylation peaks during synaptogenesis, with a striking reduction in activation between P14 and P17 just before pruning. In vitro analysis of postnatal neocortical neurons assessed the roles of intracellular signaling following MET activation. There is rapid, HGF‐induced phosphorylation of MET, ERK1/2, and Akt that is accompanied by two major morphological changes: increases in total dendritic growth and synapse density. Selective inhibition of each signaling pathway altered only one of the two distinct events. MAPK/ERK pathway inhibition significantly reduced the HGF‐induced increase in dendritic length, but had no effect on synapse density. In contrast, inhibition of the PI3K/Akt pathway reduced HGF‐induced increases in synapse density, with no effect on dendritic length. The data reveal a key role for MET activation during the period of neocortical neuron growth and synaptogenesis, with distinct biological outcomes mediated via discrete MET‐linked intracellular signaling pathways in the same neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1160–1181, 2016     

Isoforms of Aldehyde Dehydrogenase in the Brain Structures of Rats with Different Inclinations to Ethanol Consumption

We measured the levels of activity of aldehyde dehydrogenase (AdhDH, EC 1.2.1.3) manifested at different concentrations of acetaldehyde (AcAdh) in cytosol fractions from the tissues of the hypothalamus, midbrain, and neocortex of rats preferring an ethanol solution or pure water as liquids for drinking (ethanol- and water-preferring, EP and WP groups, respectively). Two AdhDH isoforms, with a high and a low affinity for AcAdh, were identified in the above brain structures. An AdhDH-1 isoform characterized by a higher affinity for AcAdh and a low value of the apparent Michaelis constant (K _m) was found in all studied brain structures of the EP rats. An analogous AdhDH-1 isoform found in cytosol fractions from the hypothalamus and midbrain of the WP rats showed a lower affinity for AcAdh and provided a lower maximum rate of reaction (V _max). In the neocortex cytosol fractions of the rats of this group, AdhDH-1 could not be identified. In EP rats, the level of AcAdh metabolism mediated by AdhDH was noticeably higher in cytosol fractions from the hypothalamus and midbrain, as compared with that in the respective fraction from the neocortex.     

Do neocortical pyramidal neurons display stochastic resonance?

Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity that has a significant impact on various electrophysiological properties and dendritic integration. Using detailed biophysical models of a morphologically reconstructed neocortical pyramidal neuron, in which synaptic background activity was simulated according to recent measurements in cat parietal cortex in vivo, we show that the responsiveness of the cell to additional periodic subthreshold stimuli can be significantly enhanced through mechanisms similar to stochastic resonance. We compare several paradigms leading to stochastic resonance-like behavior, such as varying the strength or the correlation in the background activity. A new type of resonance-like behavior was obtained when the correlation was varied, in which case the responsiveness is sensitive to the statistics rather than the strength of the noise. We suggest that this type of resonance may be relevant to information processing in the cerebral cortex.     

Morphofunctional reconstruction of the brain of <Emphasis Type="Italic">Paroxyaena pavlovi</Emphasis> (Hyaenodontidae,Creodonta) based on a natural endocranial cast

The study of a natural endocranial cast of Paroxyaena has shown that its vision was an important system of afferentation, but did not prevail over others, unlike that of Neohyaenodon. The olfaction was much better developed than in Neohyaenodon. The large gyrus prorealis suggests the presence of a long mobile nose. The well-developed sensomotoric cortex is evidence that the forepaw of Paroxyaena showed a high mobility.     

Protein Kinase C Activity is Necessary for Estrogen-Induced Erk Phosphorylation in Neocortical Explants

Our laboratory showed previously that estrogen activates ERK in neocortical cultures. To further elucidate the precise signaling sequelae that lead to estrogen-induced ERK activity, we evaluated the involvement of protein kinase C (PKC). We found that neocortical explants expressed primarily PKC gamma and PKC epsilon. Consistent with the involvement of PKC in mediating estrogen-induced ERK phosphorylation, we found that estrogen treatment induced translocation of these PKC isoforms to the plasma membrane. Importantly, inhibition of these isoforms abolished the ability of estrogen to phosphorylate ERK. While direct activation of PKC mimicked the effect of estrogen on ERK, both in pattern of activation and resulting intraneuronal distribution of ERK, PKC-induced ERK phosphorylation required the activity of MEK but not B-Raf. Collectively, these data suggest a critical role for PKC in mediating estrogen induction of ERK activation in the developing brain via a MEK-dependent but B-Raf-independent pathway.     

Neurotoxic Effect of Dexamethasone: Weakening upon the Action of Antidepressants

Dose-dependent neurotoxic effects (decrease in the amplitude of field potentials generated by neurons of the СА1 area, dentate gyrus, and dorsal striatum, but not by neurons of layers ІІ and ІІІ of the parietal cortex, recorded in slices of the rat brain) were observed 24 h after i.p. injection оf dexamethasone in doses of 7 and 20 mg/kg. Dexamethasone-induced decreases in the reactivity of glutamatergic synapses in the studied cerebral structures were weakened by a noncompetitive blocker of NMDA receptors, ketamine (30 mg/kg), and an inhibitor of tyrosine protein phosphatases, sodium vanadate (15 mg/kg), if the latter agent was injected 6 h after dexamethasone administration. The neurotoxic effect of dexamethasone was intensified by a coagonist of NMDA receptors, glycine (50 mg/kg), as well as in the case where injections of dexamethasone were combined with single injections of the antidepressant fluoxetine (20 mg/kg) but not when another antidepressant, pyrazidol, was injected in the same dose. Chronic (two weeks) injections of fluoxetine and pyrazidol weakened manifestations of dexamethasone neurotoxicity. On-regulation of NMDA receptors and suppression of expression of neurotrophins are considered probable mechanisms underlying neurotoxicity of this hormone. The effect of chronic injections of antidepressants on the respective processes is discussed. Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 312–231, July–August, 2008.     

Light enough to travel: migratory bats have smaller brains,but not larger hippocampi,than sedentary species

Migratory bird species have smaller brains than non-migratory species. The behavioural flexibility/migratory precursor hypothesis suggests that sedentary birds have larger brains to allow the behavioural flexibility required in a seasonally variable habitat. The energy trade-off hypothesis proposes that brains are heavy, energetically expensive and therefore, incompatible with migration. Here, we compared relative brain, neocortex and hippocampus volume between migratory and sedentary bats at the species-level and using phylogenetically independent contrasts. We found that migratory bats had relatively smaller brains and neocortices than sedentary species. Our results support the energy trade-off hypothesis because bats do not exhibit the same degree of flexibility in diet selection as sedentary birds. Our results also suggest that bat brain size differences are subtler than those found in birds, perhaps owing to bats'' shorter migration distances. Conversely, we found no difference in relative hippocampus volume between migratory and sedentary species, underscoring our limited understanding of the role of the hippocampus in bats.     

Transplantation of fetal neocortex in rhesus monkey

A feasibility study of neural transplantation in adult rhesus monkey was undertaken. Fresh and preserved neocortex containing multiplying and maturing neurons obtained from 55–70 gestation days were transplanted into the striatum, cerebellum and cerebral cortex of adult monkeys. Tissues were preserved for 4 days either at subzero temperature in the freezer compartment of the ordinary refrigerator in Ringer lactate or incubated in culture medium. While 2 monkeys out of 5 injected with preserved tissue had successful transplants after 4 months, all the 10 monkeys injected with fresh tissue had no transplants. The size of the two surviving transplants was small. The neurons in the transplants were mainly in clusters. Many of the cells were immature and some showed early degenerative changes. Neuronal processes were restricted to the transplants and thus showed lack of morphological integration with the host tissue. Further studies are in progress to define the nature of the embryonic tissue of primate which can grow and survive and also the role of neural grafts in functional recovery following experimental lesions of the brain regions.