Neuroscience
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Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the multifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. ⋯ Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homoeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and identify new effective therapies for these conditions.
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In addition to GABA and glutamate innervations, the globus pallidus (GP) receives dopamine afferents from the pars compacta of the substantia nigra (SNc), and in turn, sends inhibitory GABAergic efferents to the subthalamic nucleus (STN) and the pars reticulata of the substantia nigra (SNr). Nevertheless, the role of dopamine in the modulation of these pallido-subthalamic and pallido-nigral projections is not known. The present study aimed to investigate the effects of intrapallidal injection of 6-hydroxydopamine (6-OHDA) on the electrical activity of STN and SNr neurons using in vivo extracellular single unit recordings in the rat and on motor behaviors, using the "open field" actimeter and the stepping test. ⋯ Electrophysiological recordings show that 6-OHDA injection into GP significantly increased the number of bursty cells in the STN without changing the firing rate, while in the SNr neuronal firing rate decreased and the proportion of irregular cells increased. Our data provide evidence that intrapallidal injection of 6-OHDA resulted in motor deficits paralleled by changes in the firing activity of STN and SNr neurons, which mimic in large part those obtained after major dopamine depletion in the classical rat model of Parkinson's disease. They support the assumption that in addition to its action in the striatum, dopamine mediates its regulatory function at various levels of the basal ganglia circuitry, including the GP.
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Working memory (WM) training has been shown to lead to improvements in WM capacity and fluid intelligence. Given that divergent thinking loads on WM and fluid intelligence, we tested the hypothesis that WM training would improve performance and moderate neural function in the Alternate Uses Task (AUT)-a classic test of divergent thinking. We tested this hypothesis by administering the AUT in the functional magnetic resonance imaging scanner following a short regimen of WM training (experimental condition), or engagement in a choice reaction time task not expected to engage WM (active control condition). ⋯ Although the two groups did not differ in their performance on the AUT, activation was significantly lower in the experimental group in ventrolateral prefrontal and dorsolateral prefrontal cortices-two brain regions known to play dissociable and critical roles in divergent thinking. Furthermore, gain in fluid intelligence mediated the effect of training on brain activation in ventrolateral prefrontal cortex. These results indicate that a short regimen of WM training is associated with lower prefrontal activation-a marker of neural efficiency-in divergent thinking.
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Oligodendrocytes are important for not only nerve conduction but also central nervous system (CNS) development and neuronal survival in a variety of conditions. Kallikrein-related peptidase 6 (KLK6) is expressed in oligodendrocytes in the CNS and its expression is changed in several physiological and pathological conditions, especially following spinal cord injury (SCI) and experimental autoimmune encephalomyelitis. In this study, we investigated the functions of KLK6 in oligodendrocyte lineage cell development and the production of myelin proteins using KLK6-deficient (KLK6(-/-)) mice. ⋯ Expression of myelin basic protein (MBP) and oligodendrocyte-specific protein/claudin-11, major myelin proteins, was also decreased in the KLK6(-/-) spinal cord compared with the WT spinal cord at P7-21. Moreover, after SCI, the amount of MBP in the damaged spinal cords of KLK6(-/-) mice was significantly less than that in the damaged spinal cords of WT mice. These results indicate that KLK6 plays a functional role in oligodendrocyte development and the expression of myelin proteins.
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Compensatory counter-rotations of the eyes provoked by head turns are commonly attributed to the vestibulo-ocular reflex (VOR). A recent study in guinea pigs demonstrates, however, that this assumption is not always valid. During voluntary head turns, guinea pigs make highly accurate compensatory eye movements that occur with zero or even negative latencies with respect to the onset of the provoking head movements. ⋯ Anticipatory responses provide new evidence and opportunities to study the role of extra vestibular signals in motor control and sensory-motor transformations. Exercises that employ voluntary head turns are frequently used to improve visual stability in patients with vestibular hypofunction. Thus, a deeper understanding of the origin and physiology of anticipatory responses could suggest new translational approaches to rehabilitative training of patients with bilateral vestibular loss.