Satoshi Yawata, Hiroshi Tsuchida, Mineko Kengaku, and Tomoo Hirano
The glutamate receptor subunit δ2 has been an enigma. It does not fit with the functional grouping of glutamate receptors, but it is selectively expressed in cerebellar Purkinje cells (PNs) and is required for induction of long-term depression (LTD) at parallel fiber-Purkinje cell synapses. This week, Yawata et al. identified a proximal cytoplasmic domain in δ2 that is necessary for LTD and for interaction with PICK1 (protein interacting with C kinase 1). The authors transfected GluRδ2-deficient PNs with various deletion mutants. The PDZ (postsynaptic density 95/Discs large/zona occludens-1)-binding region was not required for localization to dendritic spines or for LTD. A mutant truncated after the first 21 amino acids of the C terminus rescued LTD, whereas one containing only 13 amino acids of the C terminus did not. Expression of a peptide containing amino acids C14-20 acted as a dominant negative, blocking LTD perhaps by interfering with a δ2-PICK1 interaction.
2. Growing Axons Find NG2 Cells
Zhongshu Yang, Ryusuke Suzuki, Stephen B. Daniels, Christopher B. Brunquell, Christopher J. Sala, and Akiko Nishiyama
This week, Yang et al. examined the effect on neurite outgrowth of glial cells that express the chondroitin sulfate proteoglycan NG2. The authors refer to these cells as NG2 cells, but as they differentiate into oligodendrocytes, they are more commonly called oligodendrocyte precursor cells. NG2 can inhibit neurite outgrowth, but the authors found that neurites of hippocampal neurons in short-term cultures preferred to make contact with NG2 cells rather than with a polylysine-coated surface or mature oligodendrocytes. In vivo, axonal growth cones made extensive contact with NG2 cells in the corpus callosum. Neurons extended processes on astrocytes or NG2 cells that were twice as long as those on fibroblasts or a polylysine surface. NG2 cells overexpressing NG2 did not inhibit neurite outgrowth; neither did NG2 cells with reduced NG2 expression. Thus, an attractant or adhesive role of NG2 cells appears not to depend on expression levels of NG2.
3. Explicit and Implicit Processes in Motor Learning
Pietro Mazzoni and John W. Krakauer
In this week's Journal, Mazzoni and Krakauer set up a conflict between implicit and explicit processes in visuomotor adaptation. Subjects rotated their hand to control a computer cursor that they tried to place within a target: one of eight radially arrayed circles. In a "rotation" condition, the cursor was rotated 45° counterclockwise, offsetting subject movements. In a "rotation plus strategy" condition, subjects were informed of the offset and given a strategy to cheat the system by aiming for the circle clockwise of the actual target. This cognitive strategy initially succeeded in canceling errors but ultimately failed as subjects implicitly adapted to the rotation at the expense of making correct responses. Interestingly, the rate of adaptation was the same with or without an explicit strategy. Thus, the motor system, with a mind of its own, overrides explicit strategies involving subject awareness. Sometimes it's better not to think too much, it seems.
4. Imbalanced Neural Activity in
Nicolas Mallet, Bérangère Ballion, Catherine Le Moine, and François Gonon
The loss of dopaminergic inputs to the striatum in Parkinson's disease (PD) inevitably alters the balance of neural activity in striatal projections to substantia nigra pars reticulata (direct output) and the pallidum (indirect output). This has been attributed directly to a loss of dopamine receptor stimulation (e.g., striatonigral neurons express D1 receptors, whereas striatopallidal neurons express D2 receptors). This week, Mallet et al. suggest that other network factors may also play a role. The authors examined activity of medium size spiny neurons, GABAergic projection neurons that comprise the bulk of striatal neurons. The authors made unilateral injections of 6-hydroxydopamine, rendering rats hemiparkinsonian; then, they made extracellular recordings in anesthetized animals. Striatonigral neurons were inhibited by the loss of dopaminergic input, but striatopallidal neurons were activated. This imbalance stemmed partly from decreased activity of cortical neurons that project specifically to striatonigral neurons. Feedforward inhibition from fast spiking inhibitory interneurons remained intact, thus exacerbating the activity imbalance.