http://www.biomedcentral.com/bmcneurosci/ The latest research articles published by BMC Neuroscience 2009-11-26T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: In this paper we explored thalamocortical functional connectivity in a group of eight patients suffering from peripheral neuropathic pain (diabetic pain), and compared it with that of a group of healthy subjects. We hypothesized that functional interconnections between the thalamus and cortex can be altered after years of ongoing chronic neuropathic pain. Results: Functional connectivity was studied through a resting state functional magnetic resonance imaging (fMRI) paradigm: temporal correlations between predefined regions of interest (primary somatosensory cortex, ventral posterior lateral thalamic nucleus, medial dorsal thalamic nucleus) and the rest of the brain were systematically investigated. The patient group showed decreased resting state functional connectivity between the thalamus and the cortex. Conclusions: This supports the idea that chronic pain can alter thalamocortical connections causing a disruption of thalamic feedback, and the view of chronic pain as a thalamocortical dysrhythmia. http://www.biomedcentral.com/1471-2202/10/138 Franco Cauda Katiuscia Sacco Federico D'Agata Sergio Duca Dario Cocito Giuliano Geminiani Filippo Migliorati Gianluca Isoardo BMC Neuroscience 2009, 10:138 2009-11-26T00:00:00Z doi:10.1186/1471-2202-10-138 BMC Neuroscience 1471-2202 10 138 2009-11-26T00:00:00Z PDF Background: In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond. Results: An RSN is identified in the basal ganglia and thalamus, comprising the pallidum, putamen, subthalamic nucleus and substantia nigra, with a projection also to the supplementary motor area. Participating nuclei and thalamo-cortical connection probabilities allow this network to be identified as the motor control circuit of the basal ganglia. The network was reproducibly identified across subjects, behavioural conditions (fixation, eyes closed), field strength and echo-planar imaging parameters. It shows a frequency peak at 0.025 +/- 0.007 Hz and is most similar in spectral composition to the Default Mode (DM), a network of regions that is more active at rest than during task processing. Frequency features allow the network to be classified as an RSN rather than a physiological artefact. Fluctuations in this RSN are correlated with those in the task-positive fronto-parietal network and anticorrelated with those in the DM, whose hemodynamic response it anticipates. Conclusions: Although this basal ganglia RSN has not been reported in most ICA-based studies using a similar methodology, we demonstrate that it is reproducible across subjects, common resting state conditions and imaging parameters, and show that it corresponds with the motor control circuit. This characterisation of the basal ganglia network opens a potential means to investigate the motor-related neuropathologies in which the basal ganglia are involved. http://www.biomedcentral.com/1471-2202/10/137 Simon Robinson Gianpaolo Basso Nicola Soldati Uta Sailer Jorge Jovicich Lorenzo Bruzzone Ilse Kryspin-Exner Herbert Bauer Ewald Moser BMC Neuroscience 2009, 10:137 2009-11-23T00:00:00Z doi:10.1186/1471-2202-10-137 BMC Neuroscience 1471-2202 10 137 2009-11-23T00:00:00Z PDF Background: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean=60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. Results: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho) ratio. Conclusions: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training. http://www.biomedcentral.com/1471-2202/10/136 Richard Roche Sinead Mullally Jonathan McNulty Judy Hayden Paul Brennan Colin Doherty Mary Fitzsimons Deirdre McMackin Julie Prendergast Sunita Sukumaran Maeve Mangaoang Ian Robertson Shane O'Mara BMC Neuroscience 2009, 10:136 2009-11-20T00:00:00Z doi:10.1186/1471-2202-10-136 BMC Neuroscience 1471-2202 10 136 2009-11-20T00:00:00Z PDF Background: Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid. Results: In the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection. Conclusions: These observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated. http://www.biomedcentral.com/1471-2202/10/135 Fernanda Marques Joao Sousa Giovanni Coppola Daniel Geschwind Nuno Sousa Joana Palha Margarida Correia-Neves BMC Neuroscience 2009, 10:135 2009-11-18T00:00:00Z doi:10.1186/1471-2202-10-135 BMC Neuroscience 1471-2202 10 135 2009-11-18T00:00:00Z PDF Background: PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. Results: We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. Conclusion: We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning. http://www.biomedcentral.com/1471-2202/10/134 Joe Ramos David Townsend Dawn Piarulli Stefan Kolata Kenneth Light Gregory Hale Louis Matzel BMC Neuroscience 2009, 10:134 2009-11-16T00:00:00Z doi:10.1186/1471-2202-10-134 BMC Neuroscience 1471-2202 10 134 2009-11-16T00:00:00Z XML Background: The impairment of the pontine reticular formation (PRF) has recently been revealed to be histopathologically connected with focal-cortical seizure induced generalized convulsive status epilepticus. To elucidate whether the impairment of the PRF is a general phenomenon during status epilepticus, the focal-cortical 4-aminopyridine (4-AP) application was compared with other epilepsy models. The presence of "dark" neurons in the PRF was investigated by the sensitive silver method of Gallyas in rats sacrificed at 3 h after focal 4-AP crystal or systemic 4-AP, pilocarpine, or kainic acid application. The behavioral signs of the developing epileptic seizures were scored in all rats. The EEG activity was recorded in eight rats. Results: Regardless of the initiating drug or method of administration, "dark" neurons were consistently found in the PRF of animals entered the later phases of status epilepticus. EEG recordings demonstrated the presence of slow oscillations (1.5-2.5 Hz) simultaneously with the appearance of giant "dark" neurons in the PRF. Conclusion: We argue that the observed slow oscillation corresponds to the late periodic epileptiform discharge phase of status epilepticus, and that the PRF may be involved in the progression of status epilepticus. http://www.biomedcentral.com/1471-2202/10/133 Peter Baracskay Viola Kiglics Katalin Kekesi Gabor Juhasz Andras Czurko BMC Neuroscience 2009, 10:133 2009-11-13T00:00:00Z doi:10.1186/1471-2202-10-133 BMC Neuroscience 1471-2202 10 133 2009-11-13T00:00:00Z XML Background: Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Results: Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. Conclusion: PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS. http://www.biomedcentral.com/1471-2202/10/132 Elisabeth Barbier Jia Bei Wang BMC Neuroscience 2009, 10:132 2009-11-13T00:00:00Z doi:10.1186/1471-2202-10-132 BMC Neuroscience 1471-2202 10 132 2009-11-13T00:00:00Z XML Background: Little is known about the roles of dendritic gap junctions (GJs) of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms. Results: Under physiological conditions, excitatory post-junctional potentials (EPJPs) interact with thalamocortical (TC) inputs within an unprecedented few milliseconds (i.e. over 200 Hz) to enhance the firing probability and synchrony of coupled fast-spiking (FS) cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: 1) rapid capacitive current (Icap) underlies the activation of voltage-gated sodium channels; 2) there was less than 2 milliseconds in which the Icap underlying TC input and EPJP was coupled effectively; 3) cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; 4) synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy. Conclusion: Dendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz). Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances. http://www.biomedcentral.com/1471-2202/10/131 Qian-Quan Sun BMC Neuroscience 2009, 10:131 2009-10-29T00:00:00Z doi:10.1186/1471-2202-10-131 BMC Neuroscience 1471-2202 10 131 2009-10-29T00:00:00Z XML Background: Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival. Results: In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival. Conclusion: Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease. http://www.biomedcentral.com/1471-2202/10/130 Cara Ryan David Baranowski Babykumari Chitramuthu Suneil Malik Zhi Li Mingju Cao Sandra Minotti Heather Durham Denis Kay Christopher Shaw Hugh Bennett Andrew Bateman BMC Neuroscience 2009, 10:130 2009-10-27T00:00:00Z doi:10.1186/1471-2202-10-130 BMC Neuroscience 1471-2202 10 130 2009-10-27T00:00:00Z XML Background: Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal. Results: Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin. Conclusion: We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism. http://www.biomedcentral.com/1471-2202/10/129 Pawel Olszewski Robert Fredriksson Agnieszka Olszewska Olga Stephansson Johan Alsio Katarzyna Radomska Allen Levine Helgi Schioth BMC Neuroscience 2009, 10:129 2009-10-27T00:00:00Z doi:10.1186/1471-2202-10-129 BMC Neuroscience 1471-2202 10 129 2009-10-27T00:00:00Z XML