Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

<p>Abstract</p> <p>Background</p> <p>Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR) system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1) if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2) if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR.</p> <p>The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP) in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO₂laser heat pulses.</p> <p>Results</p> <p>While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different.</p> <p>Conclusion</p> <p>Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.</p

Plasticity in mice nociceptive spinal circuits -role of cell adhesion molecules.

Introduction: To understand the function of the genes and their products in the pain system, studies will have to deal with complex issues related to intercellular communication, e.g. plasticity in neuronal networks. To provide a basis for such studies, the present thesis compares basic features of the nociceptive spinal systems including the organization of nociceptive withdrawal reflexes (NWR), laminar organization of the nociceptive C-fibre input to the spinal cord and plastic mechanisms in the mouse and rat. On this basis, the role of adhesion molecules, in particular L1 adhesion molecules, in the nociceptive system is analyzed for the first time by using mutated mice. Results: It is confirmed that sensorimotor transformations performed by the NWR circuits abide the same principles as in the rat, at least for two of the wild-type mouse strains tested. This finding indicates that mice NWR has a modular organization as previously demonstrated in the rat. Interestingly, mouse strains with a deficit in LTP mechanisms also exhibit a deficient sensorimotor transformation, suggesting that LTP mechanisms are involved in the developmental mechanisms that fine-tune the NWR. Furthermore, basic features such as nociceptive C-fibre evoked field potentials and response characteristics like short term potentiation in deep dorsal horn neurones appear to be very similar in mouse and rat. By contrast, marked differences were found in the properties of nociceptive transmission in the superficial laminae. In particular, apparently normal wild type mice seem to lack both short and long term potentiation in the first order synapses, mechanisms that are powerful in the rat. These findings suggest that the current view on the locus of the central sensitization mechanisms needs to be reconsidered. In the second part of the thesis, the role of the cell adhesion molecule L1 in the pain system was studied in mutated mice. Interestingly, these animals were found to be almost analgesic. This hypoalgesia is not due to a general lack of nociceptive input to the spinal cord as evidenced by a normal termination pattern of C fibres and C fibre evoked potentials in the superficial laminae in L1 deficient mice. Instead, a selective defect in the nociceptive transmission to the deeper laminae of the dorsal horn and a markedly reduced wind-up in the WDR neurones were found. Conclusions: The present thesis demonstrates that there are important differences in plastic mechanisms in the spinal nociceptive pathways in the mouse and rat. In addition, it points to a key role of adhesion molecules in pain transmission. This work was supported by grants from the Swedish Research Council (M) (Proj no 1013), Kocks Foundation, Medical Faculty of Lund

Konstruktionen av den icke önskvärda medborgaren : En diskursanalys av tjugo stycken tidningsartiklar i svensk kvällspress som behandlar övervikt och fetma

Media påverkar alla som tar del av det konstanta mediabruset och påverkar människor på olika sätt. Texter skrivs oftast med en avsikt att informera, påverka, underhålla eller sälja. Syftet med denna studie var att undersöka hur kvällstidningar konstruerar bilden av överviktiga och feta. Med hjälp av diskursanalys analyserade vi tjugo stycken artiklar från Sveriges två största kvällstidningar, aftonbladet och expressen, som publicerats online senaste året. Förutom de verktyg som en diskursanalys tillbjuder användes Foucaults teorier om biopolitik. Resultatet visar att det är en mångfacetterad bild av ansvar och kunskap som målas upp där både samhället och de som bor i det tilldelas ansvar för de faktorer som orsakar övervikt och fetma. Tidningarna beskriver överviktiga och feta som glufsande, okunniga varelser samt att det beskrivs vara ett problem att väga för mycket eller för lite. Även att man som medborgare bör ha kunskap om detta problem. Genom att koppla vissa beteenden till konsekvenser skapas en bild av att det finns önskvärda och därmed icke önskvärda beteenden. Detta ger en bild av att vissa medborgare är önskvärda och andra inte är det då dessa beteenden inte bidrar till att öka nyttan, effektiviteten eller produktiviteten i samhället.   

For each muscle, responses on stimulation were normalized and expressed as percentage of the maximal response

The receptive fields were divided into zones of maximal sensitivity (70–100% of maximum), medium sensitivity, (30–70% of maximum) and low sensitivity (< 30% of maximum) and presented in different colours, dark red, maximal sensitivity, yellow, low sensitivity. The mean ± SD of the Spearman correlation for receptive fields are presented. The mean values from five consecutive mappings in each muscle were used for correlation analysis. Raw data EMG recordings from m. peroneus longus are shown on each side. The upper recordings show activity from the stimulated focus area for the respective muscles. The recordings shown in the lower pictures illustrate muscle activity when stimulated peripheral to the focus area for respective muscle. Time points (-100 ms and 900 ms with respect to start of stimulation) are shown below each graph, the horizontal dashed line indicates the threshold for counting spikes and the vertical dashed line shows the time of stimulation onset.<p><b>Copyright information:</b></p><p>Taken from "Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains"</p><p>http://www.biomedcentral.com/1471-2202/9/45</p><p>BMC Neuroscience 2008;9():45-45.</p><p>Published online 21 May 2008</p><p>PMCID:PMC2409357.</p><p></p

Can histology solve the riddle of non-functioning electrodes; factors influencing the biocompatibillity of brain machine interfaces.

Neural interfaces hold great promise to become invaluable clinical and diagnostic tools in the near future. However, the biocompatibility and the long-term stability of the implanted interfaces are far from optimized. There are several factors that need to be addressed and standardized when improving the long-term success of an implanted electrode. We have chosen to focus on three key factors when evaluating the evoked tissue responses after electrode implantation into the brain: implant size, fixation mode, and evaluation period. Further, we show results from an ultrathin multichannel wire electrode that has been implanted in the rat cerebral cortex for 1 year. To improve biocompatibility of implanted electrodes, we would like to suggest that free-floating, very small, flexible, and, in time, wireless electrodes would elicit a diminished cell encapsulation. We would also like to suggest standardized methods for the electrode design, the electrode implantation method, and the analyses of cell reactions after implantation into the CNS in order to improve the long-term success of implanted neural interfaces

The C-fibre latency is presented as the median and the error bars indicate interquartile range

When there was no muscle activity the latency was set to 400 ms. The data are compensated for differences in afferent fibre length. The shortest latency is normally found in the focus of the receptive fields. Note the small differences in latency between stimulation sites in the 129S6/SvEvTac strain as compared to the other mouse strains.<p><b>Copyright information:</b></p><p>Taken from "Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains"</p><p>http://www.biomedcentral.com/1471-2202/9/45</p><p>BMC Neuroscience 2008;9():45-45.</p><p>Published online 21 May 2008</p><p>PMCID:PMC2409357.</p><p></p

3D microelectrode cluster and stimulation paradigm yield powerful analgesia without noticeable adverse effects

The lack of satisfactory treatment for persistent pain profoundly impairs the quality of life for many patients. Stimulation of brainstem pain control systems can trigger powerful analgesia, but their complex network organization frequently prevents separation of analgesia from side effects. To overcome this long-standing challenge, we developed a biocompatible gelatin-embedded cluster of ultrathin microelectrodes that enables fine-tuned, high-definition three-dimensional stimulation in periaqueductal gray/dorsal raphe nucleus in awake rats. Analgesia was assessed from both motor reactions and intracortical signals, corresponding to pain-related signals in humans. We could select an individual-specific subset of microelectrodes in each animal that reliably provided strong pain inhibition during normal and hyperalgesia conditions, without noticeable behavioral side effects. Gait, spontaneous cortical activity at rest, and cortical tactile responses were minimally affected, indicating a highly selective action. In conclusion, our developed biocompatible microelectrode cluster and stimulation paradigm reliably enabled powerful, fine-tuned, and selective analgesia without noticeable side effects