Cognitive neuroscience

Conjunctive representation of position, direction, and velocity in entorhinal cortex. Sargolini, F. et al. Science 312, 758–762 (2006)

Grid cells in the medial entorhinal cortex (MEC) form part of a spatial coordinate system for navigation. Other cells in the MEC encode information about head direction. By studying the activity of MEC neurons in rats as they explored a two-dimensional environment, Sargolini et al. showed that these cell types are co-localized in layers III and V of the MEC, in which some grid cells are directionally tuned and some head direction cells have grid correlates. The authors propose that cells with conjunctive properties facilitate the integration of directional, positional and translational information during self-motion-based navigation.

Neurodegenerative diseases

Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Clark, I. E. et al. Nature 3 May 2006 10.1038/nature04779

Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Park, J. et al. Nature 3 May 2006 10.1038/nature04788

Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson's disease (PD) because environmental mitochondrial toxins cause PD-like pathology. The recent finding that mutations in PTEN-induced kinase 1 (PINK1), which encodes a mitochondrial kinase, cause familial PD, has added weight to this theory. Two groups now show that Drosophila pink1 is crucial for mitochondrial function and acts upstream of another PD-associated gene, parkin. Clark et al. describe pink1-null flies with male sterility, apoptotic muscle degeneration and increased sensitivity to oxidative and other stresses. Mitochondria in these flies had fragmented cristae, with some appearing almost hollow. Expression of human PINK1 rescued the pink1-null phenotype, indicating functional conservation. pink1 loss-of-function mutants generated by Park et al. exhibited degeneration of muscle and dopaminergic neurons, as well as locomotive defects. Mitochondria were grossly enlarged and severely impaired. Interestingly, both groups noticed that pink1-mutant flies had a similar phenotype to flies lacking functional parkin — an E3 ubiquitin ligase — and that parkin overexpression could rescue the pink1 mutant phenotype.

Cell biology of the neuron

α3Na+/K+-ATPase is a neuronal receptor for agrin. Hilgenberg, L. G. W. et al. Cell 125, 359–369 (2006)

Agrin is required for the clustering of acetylcholine receptors at the developing neuromuscular junction, a function that is mediated by its interaction with the receptor tyrosine kinase MuSK. Agrin has also been implicated in synapse formation, calcium homeostasis and neuronal activity, but the receptor in the brain that mediates these functions has remained unknown. Now, Hilgenberg et al. show that agrin binds to and inhibits the α3 subunit of the Na+/K+-ATPase in CNS neurons, thereby providing a mechanism for agrin to regulate neuronal activity in the CNS.