Cellular/Molecular
Loss of 4E-BP2 Does Not Increase Translation Universally
Israeli Ran, Christos G. Gkogkas, Cristina Vasuta, Maylis Tartas, Arkady Khoutorsky, et al.
(see pages 1872–1886)
Memory formation requires synthesis of new proteins to modify synaptic structure. In the absence of plasticity-inducing stimulation, protein translation is repressed at hippocampal synapses by the eukaryotic initiation factor 4E-binding protein-2 (4E-BP2), which prevents ribosome assembly on mRNAs. During the late phase of long-term potentiation (L-LTP), the mammalian target of rapamycin (mTOR) phosphorylates 4E-BP2, which causes 4E-BP2 to dissociate from its targets, allowing protein synthesis to proceed. In mice lacking 4E-BP2, the basal amplitude and frequency of AMPAergic miniature EPSCs is elevated and LTP can be induced with minimal stimulation, but normal induction protocols fail to induce L-LTP. Ran et al. extend these findings, showing that 4E-BP2 knock-out increased dendritic spine density and eliminated the mTOR dependence of L-LTP. Interestingly, loss of 4E-BP2 did not increase translation of all synaptic proteins: translation of AMPA receptor subunits GluA1 and GluA2 increased, but translation of NMDA receptor subunits, the postsynaptic density scaffolding protein PSD-95, and the activity-regulated protein Arc were unaffected.
Systems/Circuits
Neuronal Synchrony in V1 Varies with Task Demands
Nirmala Ramalingam, Justin N. J. McManus, Wu Li, and Charles D. Gilbert
(see pages 1773–1789)
Neurons in primary visual cortex are tuned to visual features such as orientation; i.e., their responses depend on the orientation of lines and edges in their receptive fields. But responses to a given stimulus are influenced by the visual context, task demands, and attention. To investigate these influences, Ramalingam et al. presented monkeys with stimuli consisting of a central line segment flanked by two parallel and two collinear segments, and they recorded responses of neurons encoding the center segment as animals performed tasks requiring attention to either the parallel or the collinear flanks. The position of parallel flanks modulated responses to the central segment more when the task required attention to those flanks than when the task required attention to the collinear pair, and vice versa. Task-dependent modulation did not appear to result from enhancement or suppression of firing in neurons encoding flanking segments, but rather from changes in the synchrony of firing between neurons encoding the center bar and those encoding the flanks.
Behavioral/Cognitive
Attention Rapidly Enhances Responses in Human Auditory Cortex
Sandra Da Costa, Wietske van der Zwaag, Lee M. Miller, Stephanie Clarke, and Melissa Saenz
(see pages 1858–1863)
Studies of visual attention indicate that attention to a particular feature modulates the responses of neurons tuned to that feature. For example, red-tuned neurons fire more if the animal is looking for red stimuli than if the animal is looking for blue stimuli. Studies in rats and ferrets have suggested that auditory attention has similar effects on neuronal response properties. Data from Da Costa et al. support this hypothesis. After high-resolution (1.5 mm) functional magnetic resonance imaging (fMRI) was used to map frequency tuning in human primary auditory cortex, subjects were presented with simultaneous sequences of low- and high-frequency tones, one in each ear. Subjects were asked to switch their attention repeatedly from one tone to the other. As attention shifted, the magnitude of fMRI signals rapidly changed in areas of auditory cortex tuned to each tone: responses in areas tuned to a tone were greater when subjects' attended to that tone than when subjects attended to the nonpreferred tone.
Neurobiology of Disease
Increasing Rod Numbers Reduces Remodeling after Cone Loss
Carole J. Saade, Karen Alvarez-Delfin, and James M. Fadool
(see pages 1804–1814)
In retinitis pigmentosa, rods degenerate, leading to night blindness and constriction of the visual field. Loss of rods results in remodeling of retinal circuitry, and after extensive rod loss, cones begin to degenerate. Rods outnumber cones 20:1 in the human retina, but cones predominate in the retina of larval zebrafish. A mutation (Xops:mCFPq13) that causes rod loss in larval zebrafish does not lead to secondary loss of cones; but a mutation that causes primary cone loss (pde6cw59) causes secondary rod degeneration. Additionally, Saade et al. found that bipolar cell processes projected ectopically in pde6cw59 larvae, but not in Xops:mCFPq13 larvae. Interestingly, as pde6cw59 larvae mature, rods continue to be born, and later-born rods survive; ectopic processes were not found in these fish. Similarly, introducing a mutation that increases rod generation in pde6cw59 larvae not only increased rod survival but also reduced remodeling of bipolar cell dendrites. These data suggest that maintaining photoreceptor density not only increases their viability, but also can prevent circuit remodeling.
ON bipolar cell axons (green) extend ectopically into the ganglion cell (red) layer after cone degeneration in zebrafish larvae. See the article by Saade et al. for details.
