Progress in brain research
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Currently, assessment of new drug efficacy in glaucoma relies on conventional perimetry to monitor visual field changes. However, visual field defects cannot be detected until 20-40% of retinal ganglion cells (RGCs), the key cells implicated in the development of irreversible blindness in glaucoma, have been lost. We have recently developed a new, noninvasive real-time imaging technology, which is named DARC (detection of apoptosing retinal cells), to visualize single RGC undergoing apoptosis, the earliest sign of glaucoma. ⋯ Using DARC, we have assessed different neuroprotective therapies in glaucoma-related animal models and demonstrated DARC to be a useful tool in screening neuroprotective strategies. DARC will potentially provide a meaningful clinical end point that is based on the direct assessment of the RGC death process, not only being useful in assessing treatment efficacy, but also leading to the early identification of patients with glaucoma. Clinical trials of DARC in glaucoma patients are due to start in 2008.
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Based on electrophysiological, neurochemical and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) and dopamine (DA) function to promote waking (W) and to inhibit slow wave sleep (SWS) and/or rapid-eye-movement sleep (REMS). Serotonergic neurons of the dorsal raphe nucleus (DRN) fire at a steady rate during W, decrease their firing during SWS and virtually cease activity during REMS. On the other hand, DA cells in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) do not change their mean firing rate across the sleep-wake cycle. ⋯ Thus, depending on the receptor subtype involved, 5-HT either facilitates or inhibits the functioning of DA cells. On the other hand, activation of DA D(2)-like receptors in the DRN increases the activity of 5-HT neurons. Thus, it can be speculated that local microinjection of DA and 5-HT ligands into the DRN and the VTA/SNc, respectively, would affect the actions of the corresponding neurons on sleep and W.
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Poor control of attention-related and motor processes, often associated with behavioural or cognitive impulsivity, are typical features of children and adults with attention-deficit hyperactivity disorder (ADHD). Until recently clinicians have observed little need to improve on or add to the catecholaminergic model for explaining the features of ADHD. Recent genetic and neuroimaging studies however provide evidence for separate contributions of altered dopamine (DA) and serotonin (5-HT) function in this disorder. ⋯ For these features there is clear evidence that DA and 5-HT neuronal systems can and do interact anomalously in ADHD at the level of the soma, the terminals and at a distance. Interactions mediated by macroglia are also likely. However, it remains difficult to ascribe specific mechanisms to their effects (in potentially different subgroups of patients) from this relatively new field of study that has as yet produced rather heterogeneous results.
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In primate, the M-group is a cell cluster in the rostral mesencephalon which contains premotor neurons for the levator palpebrae (LP) and upward-pulling eye muscles. It is therefore thought to play a role in lid-eye coupling during vertical saccades. To further elucidate its role, the afferents to the M-group and LP motoneurons were studied in monkeys. ⋯ This connectivity pattern supports the hypothesis that the M-group mediates lid-eye coupling during vertical upgaze, but is indirectly driven by collaterals of saccadic burst neurons in the RIMLF during lid saccades. A selective projection from the OPN area to the LP motoneurons, but not to other oculomotor neurons is reported here for the first time. The result is supported by the presence of glycinergic terminals only over LP motoneurons, and implies that a subset of OPNs may directly trigger saccade-related blinks.
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Preterm birth is a risk factor for deficits of neurological and cognitive development. Four cohort studies are reported investigating the effects of very premature birth (<32 weeks gestation) on visual, visuocognitive and visuomotor function between birth and 6-7 years of age. The first study used two measures of early visual cortical function, orientation reversal visual event-related potentials (OR-VERP) and fixation shifts under competition. ⋯ Development was generally relatively normal on language tests and on WPPSI scores. Factor analysis showed that while general cognitive ability accounted for the largest part of the variance, significant deficits, and a relationship to MRI results, were primarily in spatial, motor, attention and executive function tests. A model is proposed suggesting that the cluster of deficits seen in children born prematurely may be related to networks involving the cortical dorsal stream and its connections to parietal, frontal and hippocampal areas.