Search results for " Pathways"
showing 10 items of 621 documents
Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.
2017
Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-E…
Activation of Corticothalamic Layer 6 Cells Decreases Angular Tuning in Mouse Barrel Cortex.
2019
In the mouse whisker system, the contribution of L6 corticothalamic cells (L6 CT) to cortical and thalamic processing of the whisker deflection direction was investigated. A genetically defined population of L6 CT cells project to infragranular GABAergic interneurons that hyperpolarize neurons in somatosensory barrel cortex (BC). Optogenetic activation of these neurons switched BC to an adapted mode in which excitatory cells lost their angular tuning. In contrast, however, this was not the case with a general activation of inhibitory interneurons via optogenetic activation of Gad2-expressing cells. The decrease in angular tuning, when L6 CT cells were activated, was due to changes in cortic…
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
2018
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…
Hyperammonemia alters the mismatch negativity in the auditory evoked potential by altering functional connectivity and neurotransmission
2020
Minimal hepatic encephalopathy (MHE) is a neuropsychiatric syndrome produced by central nervous system dysfunction subsequent to liver disease. Hyperammonemia and inflammation act synergistically to alter neurotransmission, leading to the cognitive and motor alterations in MHE, which are reproduced in rat models of chronic hyperammonemia. Patients with MHE show altered functional connectivity in different neural networks and a reduced response in the cognitive potential mismatch negativity (MMN), which correlates with attention deficits. The mechanisms by which MMN is altered in MHE remain unknown. The objectives of this work are as follows: To assess if rats with chronic hyperammonemia rep…
Activation of MORs in the VTA induces changes on cFos expression in different projecting regions: Effect of inflammatory pain.
2019
Abstract Chronic pain is a worldwide major health problem and many pain-suffering patients are under opioid based therapy. Epidemiological data show that pain intensity correlates with the risk of misuse of prescription opioids, and other drugs of abuse including alcohol. This increased vulnerability to suffer Substance Use Disorders could be, in part, caused by functional changes that occur over the mesocorticolimbic system, a brain pathway involved in reward processing and addiction. Previous data in rats revealed that inflammatory pain desensitizes mu opioid receptors (MORs) in the ventral tegmental area (VTA). As a consequence, pain alters dopamine release in the nucleus accumbens (NAc)…
Search for a Minimal Set of Parameters by Assessing the Total Optimization Potential for a Dynamic Model of a Biochemical Network.
2017
Selecting an efficient small set of adjustable parameters to improve metabolic features of an organism is important for a reduction of implementation costs and risks of unpredicted side effects. In practice, to avoid the analysis of a huge combinatorial space for the possible sets of adjustable parameters, experience-, and intuition-based subsets of parameters are often chosen, possibly leaving some interesting counter-intuitive combinations of parameters unrevealed. The combinatorial scan of possible adjustable parameter combinations at the model optimization level is possible; however, the number of analyzed combinations is still limited. The total optimization potential (TOP) approach is…
pH-sensitive vibrational probe reveals a cytoplasmic protonated cluster in bacteriorhodopsin
2017
Infrared spectroscopy has been used in the past to probe the dynamics of internal proton transfer reactions taking place during the functional mechanism of proteins but has remained mostly silent to protonation changes in the aqueous medium. Here, by selectively monitoring vibrational changes of buffer molecules with a temporal resolution of 6 µs, we have traced proton release and uptake events in the light-driven proton-pump bacteriorhodopsin and correlate these to other molecular processes within the protein. We demonstrate that two distinct chemical entities contribute to the temporal evolution and spectral shape of the continuum band, an unusually broad band extending from 2,300 to well…
Intrinsic volatility of synaptic connections — a challenge to the synaptic trace theory of memory
2017
According to the synaptic trace theory of memory, activity-induced changes in the pattern of synaptic connections underlie the storage of information for long periods. In this framework, the stability of memory critically depends on the stability of the underlying synaptic connections. Surprisingly however, synaptic connections in the living brain are highly volatile, which poses a fundamental challenge to the synaptic trace theory. Here we review recent experimental evidence that link the initial formation of a memory with changes in the pattern of connectivity, but also evidence that synaptic connections are considerably volatile even in the absence of learning. Then we consider different…
Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling
2016
Summary Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually innervating non-corresponding barrels. This misrouting relied on lost axonal sensitivity toward lysophosphatidic acid (LPA), which failed to repel PRG-2-deficient thalamocortical fibers. PRG-2 electroporation in the PRG-2−/− thalamus restored the aberrant cortical innervation. We ide…
Identification of accessory olfactory system and medial amygdala in the zebrafish
2017
AbstractZebrafish larvae imprint on visual and olfactory cues of their kin on day 5 and 6 postfertilization, respectively. Only imprinted (but not non-imprinted) larvae show strongly activated crypt (and some microvillous) cells demonstrated by pERK levels after subsequent exposure to kin odor. Here, we investigate the olfactory bulb of zebrafish larvae for activated neurons located at the sole glomerulus mdG2 which receives crypt cell input. Imprinted larvae show a significantly increased activation of olfactory bulb cells compared to non-imprinted larvae after exposure to kin odor. Surprisingly, pERK activated Orthopedia-positive cell numbers in the intermediate ventral telencephalic nucl…