News tips from The Journal of Neuroscience

1. FMRP and the Polyribosome
Giovanni Stefani, Claire E. Fraser, Jennifer C. Darnell, and Robert B.Darnell
Fragile X mental retardation syndrome affects one of every 4000 males as a result of silencing of a gene encoding an RNAbinding protein. The FMR1 gene product, fragile X mental retardation protein (FMRP), associates with polyribosomes in non-neuronal cells, suggesting that its normal function is regulation of protein translation. However, FMRP association with polyribosomes has not been demonstrated in brain tissue. Now, Stefani et al. report that in cortical extracts from mice, FMRP cosediments with polyribosomes. Furthermore, in cultured neuroblastoma cells, puromycin, which specifically disrupts active translating ribosomes, disrupted large FMRP–polyribosome complexes. These studies support the idea that FMRP regulates protein translation, but many questions remain. For example, how does it affect translation and is the net effect of FMRP enhanced or depressed translation? The authors suggest that FMRP might affect translation of mRNAs already engaged in polyribosomes, perhaps making them suitable for regulation of protein synthesis-dependent synaptic plasticity.

2. Understanding Deep Brain
Stimulation in Parkinsonism
Izhar Bar-Gad, Shlomo Elias, Eilon Vaadia, and Hagai Bergman
Many successful therapies develop before the underlying mechanisms are understood. Such is the case for the treatment of Parkinsonism with high-frequency "deep brain stimulation" (DBS). Because DBS had similar effects to local ablation, total inhibition of neuronal firing seemed at first to be a likely mechanism. In this week's Journal, Bar-Gad et al. revisit this issue using microstimulation of the globus pallidus (GP) in an MPTP-injected monkey. They simultaneously stimulated and recorded from the GP, and optimized their recording to minimize stimulus artifacts. Their results suggest a complex response of units in the GP to low-frequency and high- frequency stimulation. Low-frequency stimulation often evoked triphasic responses in neurons whereas high-frequency stimulation "locked" neuronal firing to the stimulus in most neurons. Although the authors could not separate segments within the GP, their results clearly indicate that DBS disrupts activity in a manner distinct from ablation, perhaps by effectively "jamming" the abnormal activity characteristic of movement disorders such as Parkinsonism.

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