Neuroscience
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Fragile X mental retardation protein (FMRP) binds select mRNAs, functions in intracellular transport of these mRNAs and represses their translation. FMRP is highly expressed in neurons and lack of FMRP has been shown to result in dendritic dysmorphology and altered synaptic function. FMRP is known to interact with mRNAs for the Kv3.1b potassium channel which is required for neurons to fire action potentials at high rates with remarkable temporal precision. ⋯ To examine this hypothesis, we have studied normal human brainstem tissue with immunohistochemical techniques and confocal microscopy. Our results demonstrate that FMRP is widely expressed in cell bodies and dendritic arbors of neurons in the human cochlear nucleus and superior olivary complex and also that coincidence detector neurons of the medial superior olive colocalization of FMRP and Kv3.1b. We interpret these observations to suggest that the lower auditory brainstem is a potential site of dysfunction in FXS.
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We examined changes in the variability, frequency composition, and complexity of force signal from subacute to chronic stage of stroke during maintenance of isometric knee extension and compared these parameters between chronic stroke and healthy subjects. The sample included 15 healthy (65±8 years) and 23 chronic stroke subjects (65±14 years, 6-112 months post-stroke) of whom 10 (64±15 years) were also examined 11-22 days post-stroke (subacute stage). The subjects performed isometric knee extension at 10%, 20%, 30%, and 50% of peak torque for 10s (two trials each). ⋯ These results indicate a shift toward lower frequencies and a less complex physiological process underlying force control in chronic stroke. The overall results suggest the improvement in force variability from subacute to chronic stroke but without normalization in the frequency composition and complexity of the force signal. Thus, disordered structure of the force signal remains a marker of impaired motor control long after stroke occurrence despite apparent recovery in force variability.
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In humans the identification of the primary gustatory cortex (PGC) is still under debate. Neuroimaging studies indicate insula and overlying opercula as the best candidates but the exact position of the PGC within this region is not entirely clear. Moreover, inconsistencies appear when comparing results from studies using functional magnetic resonance imaging (fMRI), and gustatory event-related potentials (gERP), or gustatory event-related magnetic fields (gERMF). fMRI indicates activations in the anterior part of the insula and frontal operculum, while gERP and/or gERMF indicate activations at the transition between the parietal operculum and insula in its posterior part. ⋯ In the present study gERMF and gERP were recorded simultaneously using a whole-head system with 249 magnetometers and 32 electrodes, respectively; taste stimuli were applied using a stimulator providing excellent temporal and spatial control of the stimulus. Separate ERP and ERMF averaged waveforms were derived time-locked to the onset of the taste stimuli. The source analysis for the early time range revealed activity in the left and right anterior and mid part of the insula, where in the later time range the sources were located more in the posterior part of the insula.
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The coppery titi monkey (Callicebus cupreus) is a socially monogamous New World primate that has been studied in the field and the laboratory to investigate the behavioral neuroendocrinology of primate pair bonding and parental care. Arginine vasopressin has been shown to influence male titi monkey pair-bonding behavior, and studies are currently underway to examine the effects of oxytocin on titi monkey behavior and physiology. Here, we use receptor autoradiography to identify the distribution of arginine vasopressin 1a receptor (AVPR1a) and oxytocin receptors (OXTR) in hemispheres of titi monkey brain (n=5). ⋯ AVPR1a binding is present throughout the cortex, especially in cingulate, insular, and occipital cortices, as well as in the caudate, putamen, nucleus accumbens, central amygdala, endopiriform nucleus, hippocampus (CA4 field), globus pallidus, lateral geniculate nucleus, infundibulum, habenula, PAG, substantia nigra, olivary nucleus, hypoglossal nucleus, and cerebellum. Furthermore, we show that, in the titi monkey brain, the OXTR antagonist ALS-II-69 is highly selective for OXTR and that the AVPR1a antagonist SR49059 is highly selective for AVPR1a. Based on these results and the fact that both ALS-II-69 and SR49059 are non-peptide, small-molecule antagonists that should be capable of crossing the blood-brain barrier, these two compounds emerge as excellent candidates for the pharmacological manipulation of OXTR and AVPR1a in future behavioral experiments in titi monkeys and other primate species.
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Interactions between neurotransmitters and the immune system represent new prospects for understanding neuroinflammation and associated neurological disease. GABA is the chief inhibitory neurotransmitter but its actions on immune pathways in the brain are unclear. In the present study, we investigated GABAergic transport in conjunction with neuroinflammation in models of multiple sclerosis (MS). ⋯ In vivo GNX treatment reduced Gat-2, Cd3ε, MhcII, and Xbp-1/s expression in spinal cords following EAE induction (p<0.05), which was correlated with improved neurobehavioral outcomes and reduced neuroinflammation, demyelination and axonal injury. These findings highlight altered GABAergic transport through GAT-2 induction during neuroinflammation. GABA transport and neuroinflammation are closely coupled but regulated by GNX, pointing to GABAergic pathways as therapeutic targets in neuroinflammatory diseases.