Neuroscience
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As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for the treatment of brain disorders. Here, I review studies on mGluRs in the auditory system. ⋯ These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted.
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Previous neuroimaging studies of response inhibition have examined correlations between behavioral efficiency and brain activity, but the temporal stability of the correlations has largely been ignored. The present functional magnetic resonance imaging (fMRI) study demonstrates the temporal changes of the brain activity associated with performance efficiency that led to more robust brain-behavior correlations in a later part of the experimental sessions. Participants performed a stop-signal task requiring inhibition of inappropriate responses, where more efficient behavioral performance is reflected in a shorter stop-signal reaction time (SSRT). ⋯ In the cerebellar region that showed the greatest difference in correlations between the second and the first halves, the brain activity increased in efficient performers, whereas the brain activity decreased in poor performers. These results suggest the existence of multiple brain mechanisms that increase and decrease the brain activity depending on the behavioral efficiency of the performers. More practically, these results indicate that robust brain-behavior correlations can more effectively be detected in a later part of the experimental sessions.
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Zellweger syndrome (ZS) is a severe peroxisomal disorder caused by mutations in peroxisome biogenesis, or PEX, genes. A central hallmark of ZS is abnormal neuronal migration and neurodegeneration, which manifests as widespread neurological dysfunction. The molecular basis of ZS neuropathology is not well understood. ⋯ We demonstrate that PEX13 brain mutants display changes that reflect an abnormal serotonergic system - decreased levels of tryptophan hydroxylase-2, the rate-limiting enzyme of serotonin (5-hydroxytryptamine, 5-HT) synthesis, dysmorphic 5-HT-positive neurons, abnormal distribution of 5-HT neurons, and dystrophic serotonergic axons. The raphe nuclei region of PEX13 brain mutants also display increased levels of apoptotic cells and reactive, inflammatory gliosis. Given the role of the serotonergic system in brain development and motor control, dysfunction of this system would account in part for the observed neurological changes of PEX13 brain mutants.
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Glial cell line-derived neurotrophic factor (GDNF) exerts neurotrophic and neuroprotective effects on substantia nigra (SN) dopamine neurons and has great therapeutic potential for Parkinson's disease (PD). Hindering this potential is the fact that GDNF cannot cross the blood-brain barrier. The aim of this study was to assess the effects of GDNF administered by the intranasal route in normal rats, and in the unilateral 6-hydroxydopamine (6-OHDA) model of PD. ⋯ Three 50-μg doses given at daily intervals (1 day before, 1h before, and 1 day after 6-OHDA) provided even greater protection than single 150-μg doses. Multiple doses at short intervals may therefore provide greater neuroprotection than single bolus doses. These results demonstrate both a neurotrophic effect of intranasal GDNF in the intact SN as well as neuroprotective efficacy in the unilateral 6-OHDA model, supporting pursuit of this approach as a potential treatment for PD.
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In resting state, the dynamics of blood oxygen level-dependent signals recorded by functional magnetic resonance imaging (fMRI) showed reliable modular structures. To explore the network property, previous research used to construct an adjacency matrix by Pearson's correlation and prune it using stringent statistical threshold. However, traditional analyses may lose useful information at middle to moderate high correlation level. ⋯ Graph theoretical analyses further demonstrated that the network feature of neural pattern 1 was more local and segregate, whereas that of neural pattern 2 was more global and integrative. Our results suggest that future resting fMRI research may take the neural pattern at middle to moderate high correlation range into consideration, which has long been ignored in extant literature. The variation of neural pattern 2 could be relevant to individual characteristics of self-regulatory functions, and the disruption in its topology may underlie the pathology of several neuropsychiatric illnesses.