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A generally accepted explanation of the spiral illusion is that the receptor cells sensitive to tho specific motions being observed become ‘suppressed’ by inhibition consequent upon that stimulation. However, an original neurological model suggests that inhibition is a short-term process, whereas perception is also dependent upon longer-term ‘learning’. The model predicts that the duration of the illusion will be increased by the accumulation of ‘learned records’ of tho moving spiral. In the experiment, ‘learning sessions’ followed daily tests of duration, and an increase was demonstrated on the next day, more than 22 hours after such a session. No increase was detected where the ‘learning session’ was omitted or replaced by a ‘fatigue session‘ employing an oppositely drawn spiral. In this way the ‘learning effect’ was distinguished from ‘suppression’, or a possible improved ‘discrimination’ due to practice. The results confirm the predictions of the new model and are difficult to reconcile with the ‘suppression’ hypothesis. [ABSTRACT FROM AUTHOR]

In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and testing independent transgenic lines that overexpress NMDAR containing the type 2B subunit (NR2B) specifically in PCs. PCs of the mice that show larger NMDA-mediated currents than controls at their PF input suffer from a blockage of long-term potentiation (LTP) at their PF-PC synapses, while long-term depression (LTD) and baseline transmission are unaffected. Moreover, introducing NMDA-mediated currents affects cerebellar learning in that phase-reversal of the vestibulo-ocular reflex (VOR) is impaired. Our results suggest that under physiological circumstances PC spines lack NMDARs postsynaptically at their PF input so as to allow LTP to contribute to motor learning.

Cerebellar motor learning is required to obtain procedural skills. Studies have provided supportive evidence for a potential role of kinase-mediated long-term depression (LTD) at the parallel fiber to Purkinje cell synapse in cerebellar learning. Recently, phosphatases have been implicated in the induction of potentiation of Purkinje cell activities in vitro, but it remains to be shown whether and how phosphatase-mediated potentiation contributes to motor learning. Here, we investigated its possible role by creating and testing a Purkinje cell-specific knockout of calcium/calmodulin-activated protein-phosphatase-2B (L7-PP2B). The selective deletion of PP2B indeed abolished postsynaptic long-term potentiation in Purkinje cells and their ability to increase their excitability, whereas LTD was unaffected. The mutants showed impaired "gain-decrease" and "gain-increase" adaptation of their vestibulo-ocular reflex (VOR) as well as impaired acquisition of classical delay conditioning of their eyeblink response. Thus, our data indicate that PP2B may indeed mediate potentiation in Purkinje cells and contribute prominently to cerebellar motor learning., (2010 Elsevier Inc. All rights reserved.)

Echinoderm microtubule-associated protein (EMAP) is the major microtubule binding protein in dividing sea urchin (Strongylocentrotus purpuratus) eggs. Echinoderm microtubule-associated protein like protein 4 (Eml4, restrictedly overexpressed proliferation-associated protein 120 kDa (Ropp120)) is one of the five mammalian EMAP homologues, the cellular function of which remains to be elucidated. In our first set of experiments we determined the spatio-temporal expression pattern of Eml4 in mouse brain. Our results demonstrate that Eml4 is a highly developmentally regulated gene with high expression levels in the developing nervous system of E11 embryos declining to low levels in adult. Spatially, Eml4 expression becomes restricted to the olfactory bulb, hippocampus and cerebellum. Transient transfection of a fusion construct of full-length mouse Eml4 with green fluorescent protein (GFP-Eml4) into Cos7 and HeLa cells resulted in colocalization of GFP-Eml4 with microtubules. This colocalization was observed both with microtubules of non-dividing cells and with the mitotic spindle of dividing cells. In addition, transient overexpression of GFP-Eml4 in Cos7 cells resulted in microtubules that were resistant to nocodazole treatment suggesting that Eml4 stabilizes microtubules. A consequence of microtubule stabilization is a net reduction in the amount of free tubulin. Microtubule stabilizing proteins therefore are expected to indirectly decrease the microtubule growth rate. Indeed, transient transfection of GFP-Eml4 resulted in a marked decrease in the microtubule growth rate, which is in line with our hypothesis that Eml4 functions as a microtubule stabilizing protein. In summary, our results suggest that Eml4 is a developmentally regulated protein that colocalizes with and stabilizes microtubules.

Despite loss of centrally mediated sympathetic vasoconstriction to the legs, spinal cord-injured individuals cope surprisingly well with an orthostatic challenge. This study assessed changes in leg vascular resistance following head-up tilt in healthy (C) and in paraplegic (P) individuals. After 10 min of supine rest, subjects were tilted 30 degrees head-up. Mean arterial pressure (MAP) and total peripheral resistance (TPR) increased in C (MAP from 76.7 +/ -6.6 mmHg to 80.6 +/- 8.2 mmHg; TPR from 1.12 +/- 0.26 AU to 1.19 +/ -0.31 AU) while both remained unchanged in P. Echo Doppler ultrasound determined red blood cell velocity in the femoral artery, which decreased (P from 18.9+/-6.2 cm/s to 12.5 +/- 4.5 cm/s, P = 0.001; C from 16.3 +/- 6.2 cm/s to 10.8 +/- 5.0 cm/s, P = 0.001) and leg vascular resistance, which increased (P from 402 +/- 137 AU to 643 +/- 274 AU, P = 0.001; C from 238 +/- 68 AU to 400 +/- 122 AU, P = 0.003) from supine to upright. The present study shows that independent of supraspinal sympathetic control, humans are able to increase leg vascular resistance and maintain blood pressure during head-up tilt.

Despite the loss of centrally mediated sympathetic vasoconstriction, spinal cord-injured (SCI) individuals cope surprisingly well with orthostatic challenges. In the pathophysiology of this intriguing observation spinal sympathetic-, veno-arteriolar-(VAR), and myogenic reflexes seem to play a role. The purpose of this study was to assess whether central (stroke volume, heart rate, blood pressure and total peripheral resistance) and peripheral (leg blood flow, leg vascular resistance and femoral arterial diameter) hemodynamic responses to head-up tilt are different in two groups of SCI patients, i. e., SCI individuals with upper motor neuron lesions (who have spinal reflexes, VAR and myogenic reflexes) (U; n=6) and those with lower motor neuron lesion (who have no spinal reflexes, perhaps no VAR due to nerve degeneration, but intact myogenic reflexes) (L; n=5). Ten healthy male individuals served as controls (C) (normal supraspinal sympathetic control and presence of all reflexes). After 10 min supine rest all individuals were tilted to 30 degrees head-up tilt. Red blood cell velocity (measured by echo Doppler ultrasound) in the femoral artery decreased and vascular resistance increased significantly in all three groups in the upright position compared with supine. Mean arterial pressure (MAP) remained unchanged in U and L and increased significantly in C in the upright versus supine position. The present study shows that all SCI individuals were able to maintain MAP by increasing leg vascular resistance during head-up tilt, despite nerve degeneration in L and lack of centrally mediated sympathetic control in all SCI individuals. Results of the present study suggest that not spinal reflexes but local (myogenic) reflex activity plays a pivotal role in peripheral vascular responses upon head-up tilt when central control mechanisms fail.

We have isolated a novel transcript with homology to the major microtubule-associated protein in dividing sea urchin embryos, EMAP. The protein has a predicted MW of approximately 180 kDa and we have named it Eml5 (EMAP-like protein 5). Eml5 contains 11 putative WD40 domains and 3 hydrophobic stretches of 43 aa, HELP domains, which have been suggested to be involved in microtubule binding. Eml5 appears to consist of two tandem repeats of the complete EMAP protein separated by a putative dimerization domain. Eml5 mRNA and protein is expressed at high levels in the hippocampus, cerebellum and olfactory bulb, as determined by in situ hybridization and immunocytochemistry. Eml5 transcripts can be detected in fore- and hindbrain structures from embryonic day 13 onwards. Because other EMAP-like proteins are involved in regulating microtubule dynamics, it is likely that Eml5 plays a role in the regulation of cytoskeletal rearrangements during neuronal development and in adult brain