Synaptic Transmission from Horizontal Cells to Cones Is Impaired by Loss of Connexin Hemichannels

In the vertebrate retina, horizontal cells generate the inhibitory surround of bipolar cells, an essential step in contrast enhancement. For the last decades, the mechanism involved in this inhibitory synaptic pathway has been a major controversy in retinal research. One hypothesis suggests that connexin hemichannels mediate this negative feedback signal; another suggests that feedback is mediated by protons. Mutant zebrafish were generated that lack connexin 55.5 hemichannels in horizontal cells. Whole cell voltage clamp recordings were made from isolated horizontal cells and cones in flat mount retinas. Light-induced feedback from horizontal cells to cones was reduced in mutants. A reduction of feedback was also found when horizontal cells were pharmacologically hyperpolarized but was absent when they were pharmacologically depolarized. Hemichannel currents in isolated horizontal cells showed a similar behavior. The hyperpolarization-induced hemichannel current was strongly reduced in the mutants while the depolarization-induced hemichannel current was not. Intracellular recordings were made from horizontal cells. Consistent with impaired feedback in the mutant, spectral opponent responses in horizontal cells were diminished in these animals. A behavioral assay revealed a lower contrast-sensitivity, illustrating the role of the horizontal cell to cone feedback pathway in contrast enhancement. Model simulations showed that the observed modifications of feedback can be accounted for by an ephaptic mechanism. A model for feedback, in which the number of connexin hemichannels is reduced to about 40%, fully predicts the specific asymmetric modification of feedback. To our knowledge, this is the first successful genetic interference in the feedback pathway from horizontal cells to cones. It provides direct evidence for an unconventional role of connexin hemichannels in the inhibitory synapse between horizontal cells and cones. This is an important step in resolving a long-standing debate about the unusual form of (ephaptic) synaptic transmission between horizontal cells and cones in the vertebrate retina

A dynamic model for product strategy selection

http://deepblue.lib.umich.edu/bitstream/2027.42/4569/5/bac1410.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/4569/4/bac1410.0001.001.tx

The Dynamic Effects of Planning Horizons on the Selection of Optimal Product Strategies

The selection of appropriate product strategies by firms must account for the expected long-run returns from the market a firm contemplates entering, relative to the expected long-run returns from the market it is currently serving. These expected returns must also reflect the capabilities a firm has to implement this strategy and the resulting competitive situations it will face. The mathematical techniques of Markov processes and dynamic programming are used in this paper to develop an analytic framework which will select optimal product strategies for a firm that are consistent with its capabilities, that will meet its competitive situations, and that will maximize expected returns in the long run. This model is applied to a selected set of Michigan machine tool firms. The results indicate the general importance of total firm capabilities and the greater importance of management capability over the supporting capabilities in the selection of optimal product strategies.