Neuroscience
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Experiments were done to investigate whether hypothalamic hypocretin-1 (hcrt-1; orexin-A) neurons that sent axonal projections to cardiovascular responsive sites in the nucleus of the solitary tract (NTS) co-expressed leucine-enkephalin (L-Enk), and to determine the effects of co-administration of hcrt-1 and D-Ala2,D-Leu5-Enkephalin (DADL) into NTS on mean arterial pressure (MAP) and heart rate. In the first series, in the Wistar rat the retrograde tract-tracer fluorogold (FG) was microinjected (50nl) into caudal NTS sites at which L-glutamate (0.25 M; 10 nl) elicited decreases in MAP and where fibers hcrt-1 immunoreactive fibers were observed that also contained L-Enk immunoreactivity. Of the number of hypothalamic hcrt-1 immunoreactive neurons identified ipsilateral to the NTS injection site (1207 ± 78), 32.3 ± 2.3% co-expressed L-Enk immunoreactivity and of these, 2.6 ± 1.1% were retrogradely labeled with FG. ⋯ An hcrt-1 injection immediately after the DADL injection elicited an almost twofold increase in the magnitude of the depressor and bradycardia responses compared to those elicited by hcrt-1 alone. Prior injections of the non-specific opioid receptor antagonist naloxone or the specific opioid δ-receptor antagonist ICI 154,129 significantly attenuated the cardiovascular responses to the combined hcrt-1-DADL injections. Taken together, these data suggest that activation of hypothalamic-opioidergic neuronal systems contribute to the NTS hcrt-1 induced cardiovascular responses, and that this descending hypothalamo-medullary pathway may represent the anatomical substrate by which hcrt-1/L-Enk neurons function in the coordination of autonomic-cardiovascular responses during different behavioral states.
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The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post-error adjustments leading to response slowing following an error ("post-error slowing"; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. ⋯ To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.
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Ethanol has been described as a teratogen in vertebrate development. During early stages of brain formation, ethanol affects the evagination of the optic vesicles, resulting in synophthalmia or cyclopia, phenotypes where the optic vesicles partially or totally fuse. The mechanisms by which ethanol affects the morphogenesis of the optic vesicles are however largely unknown. ⋯ We also show that the ethanol-induced cyclopic phenotype is significantly different to that observed in cyclopic mutants, suggesting a complex effect of ethanol on a variety of targets. Our results show that ethanol not only disrupts the expression pattern of genes involved in retinal morphogenesis, such as rx3 and rx1, but also disrupts the changes in cell polarity that normally occur during eye field splitting. Thus, ethylic teratology seems to be related not only to modifications in gene expression and cell death but also to alterations in cell morphology.
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Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. ⋯ We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the μ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the μ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1β, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1β. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.
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The ventromedial spinal cord of mammals contains a neural network known as the locomotor central pattern generator (CPG) which underlies the basic generation and coordination of muscle activity during walking. To understand how this neural network operates, it is necessary to identify, characterize, and map connectivity among its constituent cells. Recently, a series of studies have analyzed the activity pattern of interneurons that are rhythmically active during locomotion and suggested that they belong to one of two functional levels; one responsible for rhythm generation and the other for pattern formation. ⋯ Anatomical tracing techniques are also employed to investigate the morphological characteristics of cells belonging to each level. Results demonstrate that putative rhythm-generating cells are medially located and extend locally projecting axons, while those with activity consistent with pattern formation are located more laterally and send axonal projections to the lateral edge of the spinal cord, in the direction of the motoneuron pools. Results of this study provide insight into the detailed anatomical organization of the locomotor CPG.