Neuroscience
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Malformations of cortical development (MCDs) include many different Central Nervous System (CNS) disorders related to a complex process of cortex formation. In children with refractory epilepsy to drug treatment undergoing surgery, focal cortical dysplasia (FCD), one of the MCDs, is considered the most common structural brain lesion found. This study aimed to study the possible alterations in neural differentiation process of human induced pluripotent stem cells (hiPSCs) related to migration and synaptic aspects from fibroblasts of two individuals affected by FCD type IIb (45-year-old male and 12-year-old female) and normal individuals. ⋯ Our results showed that in all processes and groups, individuals with dysplasia presented alterations in most part of the genes in relation to control individuals. According to our results, it is suggested that the different expressions are mainly involved in alterations of the expression of receptors and capture sites, timing, coupling of synaptic vesicles with the presynaptic membrane, regulation of ion channel and synaptic exocytosis, imbalance of the apoptosis process and abnormal microtubules that may also contribute to delays in synaptogenesis. Thus, brain formation with dysplasia is probably influenced by these genes studied.
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Lamina X is localized in the spinal cord within the region surrounding the central canal and receives descending projections from the supraspinal nuclei. Norepinephrine (NE) is a neurotransmitter in descending pathways emanating from the brain stem; NE-containing fibers terminate in the spinal dorsal cord, particularly in the substantia gelatinosa (SG). NE enhances inhibitory synaptic transmission in SG neurons by activating presynaptic α1-receptors and hyperpolarizes the membranes of SG neurons by acting on α2-receptors; NE may thus act directly on SG neurons of the dorsal spinal cord and inhibit nociceptive transmission at the spinal level. ⋯ NE-induced enhancement of mIPSCs was blocked by α1A-receptor antagonists, and NE-induced outward current was blocked by α2-receptor antagonists. NE did not affect GABA- or glycine- induced outward currents. These findings are similar to those obtained from SG neurons: NE may act at presynaptic terminals of GABAergic and glycinergic interneurons on lamina X to facilitate inhibitory-transmitter release through α1A-receptor activation and directly induce inhibitory interneuron membrane hyperpolarization through α2-receptors activation.
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Selecting and moving to spatial targets are critical components of goal-directed behavior, yet their neural bases are not well understood. The superior colliculus (SC) is thought to contain a topographic map of contralateral space in which the activity of specific neuronal populations corresponds to particular spatial locations. However, these spatial representations are modulated by several decision-related variables, suggesting that they reflect information beyond simply the location of an upcoming movement. ⋯ However, in noncompetitive trials, some neurons lost their spatial selectivity and in others activity predicted movement to ipsilateral targets. Consistent with these findings, unilateral optogenetic inactivation of pre-movement SC activity ipsiversively biased competitive, but not noncompetitive, trials. Incorporating these results into an attractor model of SC activity points to distinct pathways for orienting movements under competitive and noncompetitive conditions, with the SC specifically required for selecting among multiple potential targets.
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It is commonly recognized that physical exercise positively affects several CNS regions and improves cognitive abilities. For example, exercise is associated with an increase in neurogenesis and facilitation of long-term potentiation in the hippocampus. Conversely, animal models for depression are associated with a decrease in neurogenesis and a reduction of long-term potentiation in the hippocampus. ⋯ Unexpectedly, in dexamethasone-exposed animals, dentate gyrus long-term potentiation was facilitated, whereas long-term potentiation in CA1 was unaffected by prenatal dexamethasone or by 10 or 21 days of voluntary running. Irrespective of age, prenatal dexamethasone and running had limited effects on synaptic transmission and presynaptic release in CA1 and dentate gyrus. In summary, running facilitates dentate gyrus long-term potentiation in adult animals that resembles the effects of prenatal dexamethasone.
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Following spinal cord trauma, axonal regeneration in the mammalian spinal cord does not occur and functional recovery may be further impeded by retrograde neuronal death. By contrast, lampreys recover after spinal cord injury (SCI) and axons re-connected to their targets in spinal cord. However, the identified reticulospinal (RS) neurons located in the lamprey brain differ in their regenerative capacities - some are good regenerators, and others are bad regenerators - despite the fact that they have analogous projection pathways. ⋯ Here we report that, after SCI, expression of RGMa mRNA was upregulated around the transection site, while its receptor Neogenin continued to be synthesized almost inclusively in the "bad-regenerating" RS neurons. Inhibition of Neogenin by MO prohibited activation of caspases and improved the survival of RS neurons at 10 weeks after SCI. These data provide new evidence in vivo that Neogenin is involved in retrograde neuronal death and failure of axonal regeneration after SCI.