Neuroscience research
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Neuroscience research · Jan 2012
Acetylcholinesterase activity in the brain of dystonia musculorum (Dst(dt-J)) mutant mice.
The dystonia musculorum (Dst(dt-J)) mutant mouse suffers from severe motor coordination deficits, characterized, among various symptoms, by a spastic ataxia and dystonic movements, indicating central defects in motor structures in addition to dystrophy of peripheral sensory tracts and partial degeneration of spinocerebellar tracts. Neurochemical alterations, notably in dopaminergic and noradrenergic systems, were previously observed in basal ganglia and cerebellum. A quantitative histochemical cartography of brain acetylcholinesterase activity in Dst(dt-J) mutants, in comparison with controls, revealed increases in the neostriatum, the habenula-interpeduncular pathway, the cholinergic pedunculopontine nucleus and its target structures, the thalamus, major regions of the basal ganglia, such as substantia nigra, ventral tegmental area, globus pallidum, and subthalamic nucleus, as well as in associated extrapyramidal regions, such as red nucleus, brainstem reticular formation, and superior colliculus. These acetylcholinesterase changes may play a role in motor deficits, particularly the dystonic symptomatology observed in the mutation.
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Neuroscience research · Nov 2011
RA-GEF-1 (Rapgef2) is essential for proper development of the midline commissures.
The cerebral hemispheres are directly connected by three major interhemispheric fibers: the corpus callosum, the anterior commissure, and the hippocampal commissure. RA-GEF-1 (also termed Rapgef2) is a guanine nucleotide exchange factor responsible for sustained activation of Rap1. We previously reported anatomical defects of the major forebrain commissures in the adult dorsal telencephalon-specific RA-GEF-1 conditional knockout (cKO) mice. ⋯ Wheat germ agglutinin-conjugated horseradish peroxidase retrograde tracing verifies the agenesis of the anterior commissure in cKO mice, and DiI anterograde tracing confirms the deviation of the fibers from their original tract. As for the hippocampal commissure, agenesis and hypoplasia are observed in its dorsal and ventral parts, respectively. These results indicate the essential role of RA-GEF-1 in the proper formation of the cerebral midline commissures.
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Neuroscience research · Nov 2011
Emotional face recognition, EMG response, and medial prefrontal activity in empathic behaviour.
One important aspect of empathy is a "resonance mechanism", which includes emotional cue detection, facial mimicry (measured by electromyography, EMG) and a specific cortical response. This study explored the convergence of these three measures of affective empathy. The twenty students who took part in the study were required to empathise with the situation by entering into the other person's situation. ⋯ Second, the MPFC was implicated in facial cue detection and the subsequent autonomic response because an impaired performance on both measures was observed when this brain area was inhibited. Third, this effect increased when negative-valenced stimuli (angry and fearful faces) were presented to the subjects. These results revealed a significant effect of the MPFC on both cue detection and facial mimicry that was distinctly related to different types of emotions.
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Neuroscience research · Nov 2011
Detection of autoantibody against extracellular epitopes of N-methyl-D-aspartate receptor by cell-based assay.
The concept of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a severe, potentially lethal, treatment-responsive disorder, mediated by autoantibodies against NMDAR was proposed. Because paraneoplastic anti-NMDAR encephalitis has a better prognosis after tumor resection and immunotherapy, rapid quantitative systems for detecting functional autoantibodies against extracellular epitopes of NMDAR are necessary. To detect autoantibodies recognizing extracellular epitopes of NMDAR, we stably expressed mutant NMDAR that decreases Ca(2+) permeability on a heterologous cell surface without any antagonist. ⋯ Furthermore, we were able to express mutant GluRζ1(NR1, GluN1) subunit of NMDAR alone on the cell surface and obtained direct evidence of the presence of autoantibodies recognizing extracellular epitopes of GluRζ1 and the induction of internalization by autoantibodies in serum and CSF from patients. The specificity of on-cell Western analysis was improved at 37°C. The combination of this rapid quantitative assay using our on-cell western analysis, detailed analysis of extracellular epitopes of NMDAR, and internalization assay of NMDAR will be valuable for the diagnosis, evaluation of clinical treatments, and follow-up of anti-NMDAR encephalitis.
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Neuroscience research · Oct 2011
Comparative StudyGlycine inhibits startle-mediating neurons in the caudal pontine reticular formation but is not involved in synaptic depression underlying short-term habituation of startle.
The mammalian startle response is controlled by glycine inhibition in the spinal cord. Evidence for additional glycine inhibition on the level of the brainstem, namely in the caudal pontine reticular nucleus (PnC), is controversial. Startle mediating PnC neurons receive fast input from sensory pathways and project to cranial and spinal motoneurons. ⋯ Strychnine reversed all glycine effects, but had no effect on PnC neurons itself. Thus, we found no evidence for a tonic glycine inhibition or for glycine activation within the primary startle pathway indicating that baseline startle reactions are unlikely to be controlled by glycine in the PnC. Most importantly, synaptic depression underlying short-term habituation was not affected by glycine or strychnine.