Journal of Integrative Neuroscience

The mediodorsal (MD) thalamic nucleus provides information from subcortical structures to the prefrontal cortex. The human MD thalamic nucleus has been implicated in a great variety of different clinical conditions and normal functions ranging from schizophrenia, Parkinsonism and epilepsy to many cognitive functions. In the rat the MD thalamic nucleus is divided into three cytoarchitectonic sectors whereas in the primates it is divided into two; medial one-third (magnocellular) and lateral two-thirds further the lateral sector is divided into pars parvocellularis pars multiformis, pars fasciculosa and pars caudalis. In this study we used a retrograde tracer, fluoro-gold (FG) to evaluate some of the afferents reaching the lateral sector of the MD (MDl) thalamic nucleus. The results of the present study have shown that MDl receives afferent connections from the lateral cerebellar nucleus (dentate nucleus), substantia nigra pars reticulata (SNR) and zona incerta (ZI). Subsequent to FG injections into the MDl, labeled cells were observed mainly bilaterally but were sparser on the contralateral side than ipsilaterally from each of the three structures listed. All three afferents showed a topographical organization. The labeled neurons were localized at the dorsomedial aspect of the lateral cerebellar nucleus, the dorsoventral aspect of the SNR and in the dorsal sector of the ZI. The lateral cerebellar nucleus reached the MDl via the superior cerebellar peduncle. No other deep cerebellar nuclei showed labeled cells. There were no labeled cells in the substantia nigra pars compacta (SNC). Although the three regions identified here are recognized as having motor functions, the connections to MD suggest that their outputs also play a role in cognitive or other higher cortical functions.

The aim of this study was to evaluate the validity of the model that could produce reproducible and persistent motor weakness and define the accurate tasks and testing parameters for longitudinal assessment of neurological deficits after traumatic brain injury (TBI). We compared the effects of two rat models that suffered different controlled cortical impact (CCI) injury, as well as extensive motor cortex resection model, on behavior recovery and brain morphology. Behavioral tests including the skilled reaching task, limb-use asymmetry test and the grasping test were employed to evaluate neurofunctional recovery from pre- to 12 weeks after the injury. The results demonstrated that all the rats in four groups showed spontaneous functional improvement with the past of time after surgery, especially in rats with mild and moderate CCI injury. At the end of the experiment, the animals' performance reached preoperative base lines on reaching task and limb-use asymmetry test in mild and moderate groups, while severe motor weakness could be observed in rats with severe CCI injury, as well as rats with extended motor cortex resection. Overall, the results of this study indicated that both models with severe CCI injury and extended resection of the motor cortex developed reproducible and long-lasting motor weakness, comparable in severity and duration and identified skilled reaching task, as well as limb-use asymmetry test, as sensitive assessments for slight neurological deficits after brain injury. This will help to provide the basis for further research of the processes after the TBI and development of novel therapies.

To investigate the conflict processing in posttraumatic stress disorder (PTSD) patients, we conducted the classical Stroop task by recording event-related potentials. Although the reaction time was overall slower for PTSD patients than healthy age-matched control group, the Stroop-interference effect of reaction time did not differ between the two groups. Compared with normal controls, the interference effects of N2 and N450 components were larger and the interference effect of slow potential component disappeared in PTSD. These data indicated the dysfunction of conflict processing in individuals with PTSD.

Chronic morphine exposure leads to tolerance, which limits the clinical use of this potent analgesic in the treatment of severe and chronic pain. Compelling evidence suggest that neuro-immune activation (pro-inflammatory cytokines including IL-1β, IL-6 and TNF) as well as neuro-inflammation have been shown to mediate the development of morphine analgesic tolerance. Toll-like receptors (TLRs), especially TLR-4, have also been reported to contribute to the development of morphine analgesic tolerance. Besides, mitogen-activated protein kinases (MAPKs; especially p38 MAPK and c-Jun N-terminal kinase), as well as nuclear factor-κB (NF-κB) modulate the development of morphine antinociceptive tolerance. Hence, we hypothesis the possible involvement of myeloid differentiation primary response protein 88 (MyD88), a key adaptor protein for the TLR and IL-1R families, in the development of tolerance to morphine-induced analgesia. Our study demonstrated that chronic intrathecal morphine injection led to a robust increase of MyD88 expression in rat spinal cord. Sustained elevation of MyD88 may play a role in modulating the development of morphine antinociceptive tolerance.

GABA_A receptors (GABA_ARs) are hetero-pentameric chloride channels and the primary sites for fast synaptic inhibition. We have expressed recombinant γ2 and δ subunits of GABA_ARs in cultured hippocampal neurons to analyze the membrane targeting of synaptic and extra-synaptic GABA_ARs, a phenomenon not well understood. Our data demonstrate that the synaptic targeting of γ2-containing GABA_ARs (γ2-GABA_ARs) does not depend on the cytoplasmic loop of γ2 subunit, in parallel with previous findings, showing that the synaptic localization of γ2-GABA_ARs requires the TM4 domain of γ2 rather than the large cytoplasmic loop. On the other hand, we showed here that the extrasynaptic targeting of the δ-containing GABA_ARs (δ-GABA_ARs) depends on the cytoplasmic loop of δ subunit via an active or a passive mechanism. We also show that the amino acid sequences of δ loop is highly conserved across the whole span of vertebrate evolution suggesting an active role of δ loop in extra-synaptic targeting of corresponding receptor subtypes.

Epilepsy is a serious neurodegenerative disorder with a high incidence and a variety of presentations and causes. Studies on brain from various animal models including chronic models: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are very useful for understanding the fundamental mechanisms associated with human epilepsy. Individual regions of the brain have different protein composition in different conditions. Therefore, proteomic analyses of the brain compartments are preferred for the development of new therapeutic targets in different pathophysiological conditions like neurodegenerative disorders. In this study, we describe a proteomic profiling of membrane fraction of cortex tissue from epileptic GAERS and non-epileptic Wistar rat brain by two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption/ionization mass spectroscopy. Comparing the optical density of spots between groups, we found that one protein expression was significantly down-regulated (guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1) and one protein expression was significantly up-regulated (14-3-3 protein epsilon isoform) in GAERS group. Our results indicate that these proteins might have played a significant role in epilepsy and may be considered as valuable therapeutic targets in the absence of epilepsy.

Recently, the multivariate analysis methods have been widely used for predicting the human cognitive states from fMRI data. Here, we explore the possibility of predicting the human cognitive states using a pattern of brain activities associated with thinking about concrete objects. The fMRI signals in conjunction with pattern recognition methods were used for the analysis of cognitive functions associated with viewing of 60 object pictures named by the words in 12 categories. The important step in Multi Voxel Pattern Analysis (MVPA) is feature extraction and feature selection parts. In this study, the new feature selection method (accuracy method) was developed for multi-class fMRI dataset to select the informative voxels corresponding to the objects category from the whole brain voxels. Here the result of three multivariate classifiers namely, Naïve Bayes, K-nearest neighbor and support vector machine, were compared for predicting the category of presented objects from activation BOLD patterns in human whole brain. We investigated whether the multivariate classifiers are capable to find the associated regions of the brain with the visual presentation of categories of various objects. Overall Naïve Bayes classifier perfumed best and it was the best method for extracting features from the whole brain data. In addition, the results of this study indicate that thinking about different semantic categories of objects have an effect on different spatial patterns of neural activation, and so it is possible to identify the category of the objects based on the patterns of neural activation recorded during representation of object line drawing from participants with high accuracy. Finally we demonstrated that the selected brain regions that were informative for object categorization were similar across subjects and this distribution of selected voxels on the cortex may neutrally represent the various object's category properties.

Stress is any condition that seriously affects the balance of the organism physiologically and psychologically. Stress activates the hypothalamic-pituitary-adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects on different body systems including the nervous system. This study aimed to investigate the effect of acute restraint stress (ARS) on cognitive performance by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory behavior) in open field test, expression of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic receptors (D2) in the basal ganglia by gene expression and comparing the effect of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats constituted the animal model of this work and have been divided into six groups: control group, control group exposed to ARS, quetiapine group, quetiapine group exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated more neuroprotective effect for quetiapine compared to ghrelin on stress response, anxiety behavior and working spatial memory impairment due to ARS.

Configural processing is considered to be the hallmark of face expertise, which has been widely investigated by face global inversion (inversion effect) and local inversion (Thatcher effect). Using a passive detection task in which face stimuli are task-irrelevant, both the face inversion effect and the Thatcher effect on race perception of faces were investigated. We found that although the N170 inversion effect (enhanced and delayed N170 for inverted than upright condition) was similar across races of faces, Chinese participants showed a larger N170 Thatcher effect (enhanced N170 to Thatcherized faces than normal faces) for Mongoloid faces. The present data indicates the perceptual advantage of configural changes for in-group than out-group faces.