Early View Articles

Authors: Tim Rohe, Bernd Weber, Klaus Fliessbach et al.

Published: May 18, 2012, 1:13 am

Abstract: The representation of reward anticipation and reward prediction errors is the basis for reward-associated learning. The representation of whether or not a reward occurred (reward receipt) is important for decision making. Recent studies suggest that, while reward anticipation and reward prediction errors are encoded in the midbrain and the ventral striatum, reward receipts are encoded in the medial orbitofrontal cortex. In order to substantiate this functional specialization we analyzed data from an fMRI study in which 59 subjects completed two simple monetary reward paradigms. Because reward receipts and reward prediction errors were correlated, a statistical model comparison was applied separating the effects of the two. Reward prediction error fitted BOLD responses significantly better than reward receipt in the midbrain and the ventral striatum. Conversely, reward receipt fitted BOLD responses better in the orbitofrontal cortex. Activation related to reward anticipation was found in the orbitofrontal cortex. The results confirm a functional specialization of behaviorally important aspects of reward processing within the mesolimbic dopaminergic system.During reward feedback, reward prediction errors due to an unexpectedly received or omitted reward predict BOLD responses better than simple reward receipt in the midbrain and the ventral striatum. Conversely, reward receipt fits the BOLD response better than reward prediction error in the medial orbitofrontal cortex. This finding corroborates an important functional specialization of these reward related processes within the dopaminergic system.

Authors: F. McGlone, H. Olausson, J. A. Boyle, M. Jones-Gotman, C. Dancer, S. Guest, G. Essick et al.

Published: May 18, 2012, 1:10 am

Abstract: Previous functional magnetic resonance imaging studies in two rare patients, together with microneurography and psychophysical observations in healthy subjects, have demonstrated a system of mechanosensitive C-fiber tactile (CT) afferents sensitive to slowly moving stimuli. They project to the posterior insular cortex and signal pleasant aspects of touch. Importantly, CTs have not been found in the glabrous skin of the hand, yet it is commonly observed that glabrous skin touch is also perceived as pleasant. Here we asked if the brain processing of pleasant touch differs between hairy and glabrous skin by stroking the forearm and glabrous skin of the hand during positron emission tomography. The data showed that, when contrasting slow brush stroking on the forearm with slow brush stroking on the palm, there were significant activations of the posterior insular cortex and mid-anterior orbitofrontal cortex. The opposite contrast showed a significant activation of the somatosensory cortices. Although concurrent psychophysical ratings showed no differences in intensity or pleasantness ratings, a subsequent touch questionnaire in which subjects used a newly developed ‘touch perception task’ showed significant difference for the two body sites. Emotional descriptors received higher ratings on the forearm and sensory descriptors were rated more highly on the palm. The present findings are consistent with the hypothesis that pleasant touch from hairy skin, mediated by CT afferents, is processed in the limbic-related cortex and represents an innate non-learned process. In contrast, pleasant touch from glabrous skin, mediated by A-beta afferents, is processed in the somatosensory cortex and represents an analytical process dependent on previous tactile experiences.Previous fMRI studies in two rare patients, together with microneurography and psychophysical observations in healthy subjects, have demonstrated a system of mechanosensitive C-tactile afferents (CT) sensitive to slowly moving stimuli. They project to posterior insular cortex and signal pleasant aspects of touch.

Authors: Jiwon Mo, Dongmin Lee, Soontaek Hong, Seungrie Han, Hyojin Yeo, Woong Sun, Sukwoo Choi, Hyun Kim, Hyun Woo Lee et al.

Published: May 18, 2012, 1:09 am

Abstract: In neuronal development, dendritic outgrowth and arborization are important for the establishment of neural circuit formation. A previous study reported that PSD-95-interacting regulator of spine morphogenesis (Preso) formed a complex with PAK-interacting exchange factor-beta (βPix) via PSD-95/Dlg/ZO-1 (PDZ) interaction. Here, we report that Preso and its binding protein, βPix, are localized in dendritic growth cones. Knockdown and dominant-negative inhibition of Preso in cultured neurons markedly reduced the dendritic outgrowth but not branching, and led to a decrease in the intensity of βPix and F-actin in neuronal dendritic tips. Moreover, phosphatidylinositol 4,5-bisphosphate (PIP2) induced a conformational change in Preso toward the open PDZ domain and enhanced the interaction with βPix. In addition, the Preso band 4.1 protein, ezrin, radixin and moesin (FERM) domain mutant is unable to interact with PIP2 and it did not rescue the Preso-knockdown effect. These results indicate that PIP2 is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix.Preso (PSD-95-interacting regulator of spine morphogenesis) forms a complex with βPix (PAK-interacting exchange factor beta) via PDZ interaction in dendritic growth cones and its interaction is required for neuronal dendritic development through the maintenance of F-actin by activation of small GTPase signalling. Phosphatidyl inositol 4,5-bisphosphate binding to FERM domain of Preso induces its conformational change toward open PDZ domain and enhances the interaction with βPix.

Authors: Marius Widerøe, Marianne B Havnes, Tora Sund Morken, Jon Skranes, Pål-Erik Goa, Ann-Mari Brubakk et al.

Published: May 18, 2012, 1:09 am

Abstract: Doxycycline may potentially be a neuroprotective treatment for neonatal hypoxic–ischemic brain injury through its anti-inflammatory effects. The aim of this study was to examine any long-term neuroprotection by doxycycline treatment on cerebral gray and white matter. Hypoxic–ischemic brain injury was induced in 7-day-old rats. Pups were treated with either doxycycline (HI+doxy) or saline (HI+vehicle) by intraperitoneal injection at 1 h after hypoxia–ischemia (HI). At 6 h after HI, MnCl2 was injected intraperitoneally for later manganese-enhanced magnetic resonance imaging (MRI). MRI was performed with diffusion-weighted imaging on day 1 and T1-weighted imaging and diffusion tensor imaging at 7, 21 and 42 days after HI. Animals were killed after MRI on day 42 and histological examinations of the brains were performed. There was a tendency towards lower lesion volumes on diffusion maps among HI+doxy than HI+vehicle rats at 1 day after HI. Volumetric MRI showed increasing differences between groups with time after HI, with less cyst formation and less cerebral tissue loss among HI+doxy than HI+vehicle pups. HI+doxy pups had less manganese enhancement on day 7 after HI, indicating reduced inflammation. HI+doxy pups had higher fractional anisotropy on diffusion tensor imaging in major white matter tracts in the injured hemisphere than HI+vehicle pups, indicating less injury to white matter and better myelination. Histological examinations supported the MRI results. Lesion size on early MRI was highly correlated with final injury measures. In conclusion, a single dose of doxycycline reduced long-term cerebral tissue loss and white matter injury after neonatal HI, with an increasing effect of treatment with time after injury.Doxycycline may potentially be a neuroprotective treatment for neonatal hypoxic–ischemic brain injury through its anti-inflammatory effects. The aim of this study was to examine any long-term neuroprotection by doxycycline treatment on cerebral gray and white matter.

Authors: Viswanath Das, John H. Miller et al.

Published: May 18, 2012, 1:09 am

Abstract: Many cellular organelles must travel long distances in neurons to perform their specific functions, and this transport is highly dependent on the microtubule network within the axon. Hyperphosphorylation of microtubule-associated tau protein destabilizes microtubules and leads to neuronal cell death. This destabilization can be corrected in part by treatment with microtubule-stabilizing drugs such as paclitaxel and epothilone. The phosphatase inhibitor okadaic acid inhibits the outgrowth of neurites in neuronal cell cultures by hyperphosphorylating tau protein. In this study using neuronal cultures derived from the cerebral cortex of early postnatal Sprague–Dawley rats, we examined whether stabilization of microtubules by peloruside A, a microtubule-stabilizing agent that binds to a different site on β-tubulin from paclitaxel, could counter the deleterious effects of 8 h exposure to 15 nm okadaic acid. Peloruside A reversed the decrease in axonal outgrowth and branching seen in neuronal cultures treated with okadaic acid and rescued neurons from growth cone collapse. Although peloruside A had no effect on the hyperphosphorylation of tau caused by okadaic acid, it restored the levels of acetylated tubulin, a marker of stable microtubules, and reversed the okadaic acid-induced depression of growth-associated protein-43, an axonal growth regulator. Thus, microtubule-stabilizing drugs show promise as new therapeutic agents for treating damaged microtubule networks characteristic of neurodegenerative disease.Many cellular organelles must travel long distances in neurons to perform their specific functions, and this transport is highly dependent on the microtubule network within the axon. Hyperphosphorylation of microtubule-associated tau protein destabilizes microtubules and leads to neuronal cell death.