Neuroscience
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Somatosensory information from the limbs reaches the contralateral Primary Sensory Cortex (S1) with a delay of 23ms for finger, and 40ms for leg (somatosensory N20/N40). Upon arrival of this input in the cortex, motor evoked potentials (MEPs) elicited by Transcranial Magnetic Stimulation (TMS) are momentarily inhibited. This phenomenon is called 'short latency afferent inhibition (SAI)' and can be used as a tool for investigating sensorimotor interactions in the brain. ⋯ No ipsilateral SAI was detected in the lower limb (TA) at any of the tested ISIs. The delayed onset timing of ipsilateral SAI suggests that transcallosal communication mediates this inhibitory process for the upper limb. The complete absence of ipsilateral SAI in the lower limb warrants consideration of the potential limb-specific differences in demands for bilateral sensorimotor integration.
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Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. ⋯ Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors.
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Paclitaxel is a first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Previous preclinical studies indicate mitochondrial dysfunction and oxidative stress are associated with this disorder; however no direct assessment of reactive oxygen species (ROS) levels and antioxidant enzyme activity in sensory neurons following paclitaxel has been undertaken. As expected, repeated low doses of systemic paclitaxel in rats induced long-lasting pain behaviour with a delayed onset, akin to the clinical scenario. ⋯ In peripheral sensory nerves, CuZnSOD activity was increased at day 7, and at peak pain, MnSOD, CuZnSOD and GPx activity were increased. Catalase activity was unaltered in DRG and saphenous nerves. These data suggest that neuronally-derived mitochondrial ROS, accompanied with an inadequate endogenous antioxidant enzyme response, are contributory factors in paclitaxel-induced painful neuropathy.
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DTNBP1, which encodes dysbindin-1, is associated with cognitive impairment. Genetic evidence indicates that the C allele of rs117610176 leads to an increase in DTNBP-1b mRNA splicing in patients with paranoid schizophrenia. In addition, dysbindin-1B, rather than dysbindin-1A/C, exhibits a tendency toward toxic aggregation. ⋯ In addition, we used the Morris water maze task to investigate the effects of dysbindin-1B aggregation on cognition. The results demonstrated that Dys1B(+/+) mice exhibited spatial learning and memory deficits, which were accompanied by the shrinkage of apical and basal dendritic branches and the loss of dendritic spines in hippocampal CA1 neurons, as demonstrated by Golgi staining. Taken together, the results of the present study suggest that dysbindin-1B toxic aggregation might impair cognition through a dominant-negative effect on BLOC-1.
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The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. ⋯ No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis.