Nonlinear computations shaping temporal processing of precortical vision.

Computations performed by the visual pathway are constructed by neural circuits distributed over multiple stages of processing, and thus it is challenging to determine how different stages contribute on the basis of recordings from single areas. In the current article, we address this problem in the lateral geniculate nucleus (LGN), using experiments combined with nonlinear modeling capable of isolating various circuit contributions. We recorded cat LGN neurons presented with temporally modulated spots of various sizes, which drove temporally precise LGN responses. We utilized simultaneously recorded S-potentials, corresponding to the primary retinal ganglion cell (RGC) input to each LGN cell, to distinguish the computations underlying temporal precision in the retina from those in the LGN. Nonlinear models with excitatory and delayed suppressive terms were sufficient to explain temporal precision in the LGN, and we found that models of the S-potentials were nearly identical, although with a lower threshold. To determine whether additional influences shaped the response at the level of the LGN, we extended this model to use the S-potential input in combination with stimulus-driven terms to predict the LGN response. We found that the S-potential input "explained away" the major excitatory and delayed suppressive terms responsible for temporal patterning of LGN spike trains but revealed additional contributions, largely PULL suppression, to the LGN response. Using this novel combination of recordings and modeling, we were thus able to dissect multiple circuit contributions to LGN temporal responses across retina and LGN, and set the foundation for targeted study of each stage.

Nonlinearity and noise at the rod-rod bipolar cell synapse.

In the retina, rod bipolar (RBP) cells synapse with many rods, and suppression of rod outer segment and synaptic noise is necessary for their detection of rod single-photon responses (SPRs). Depending on the rods' signal-to-noise ratio (SNR), the suppression mechanism will likely eliminate some SPRs as well, resulting in decreased quantum efficiency. We examined this synapse in rabbit, where 100 rods converge onto each RBP. Suction electrode recordings showed that rabbit rod SPRs were difficult to distinguish from noise (independent SNR estimates were 2.3 and 2.8). Nonlinear transmission from rods to RBPs improved response detection (SNR = 8.7), but a large portion of the rod SPRs was discarded. For the dimmest flashes, the loss approached 90%. Despite the high rejection ratio, noise of two distinct types was apparent in the RBP traces: low-amplitude rumblings and discrete events that resembled the SPR. The SPR-like event frequency suggests that they result from thermal isomerizations of rhodopsin, which occurred at the rate 0.033/s/rod. The presence of low-amplitude noise is explained by a sigmoidal input-output relationship at the rod-RBP synapse and the input of noisy rods. The rabbit rod SNR and RBP quantum efficiency are the lowest yet reported, suggesting that the quantum efficiency of the rod-RBP synapse may depend on the SNR in rods. These results point to the possibility that fewer photoisomerizations are discarded for species such as primate, which has a higher rod SNR.

Disodium cromoglycate in the treatment of systemic mastocytosis involving only bone.

A 50-year-old woman with a 5-year history of low back pain and osteosclerosis was diagnosed as having systemic mastocytosis. She had no cutaneous or gastrointestinal manifestations of this disease. She was successfully treated with oral disodium cromoglycate. This is the first reported case of systemic mastocytosis involving only bone which responded to treatment with oral disodium cromoglycate.

Mutants of Salmonella typhimurium with an altered leucyl-transfer ribonucleic acid synthetase.

Two trifluoroleucine-resistant mutants of Salmonella typhimurium, strains CV69 and CV117, had an altered leucyl-transfer ribonucleic acid (tRNA) synthetase. The mutant enzymes had higher apparent K(m) values for leucine (ca. 10-fold) and lower specific activities (ca. twofold) than the parent enzyme when tested in crude extracts. Preparations of synthetase purified ca. 60-fold from the parent and strain CV117 differed sixfold in their leucine K(m) values. In addition, the mutant enzyme was inactivated faster than the parent enzyme at 50 C. The growth rates of strains CV69 and CV117 at 37 C were not significantly different from that of the parent, whereas at 42 C strain CV69 grew more slowly than the parent. Leucine-, valine-, and isoleucine-forming enzymes were partially derepressed when the mutants were grown in minimal medium; the addition of leucine repressed these enzymes to wild-type levels. During growth in minimal medium, the proportion of leucine tRNA that was charged in the mutants was about 75% of that in the parent. The properties of strain CV117 were shown to result from a single mutation located near gal at minute 18 on the genetic map. These studies suggest that leucyl-tRNA synthetase is involved in repression of the enzymes required for the synthesis of branched-chain amino acids.