Axonal topography of cortical basket cells in relation to orientation, direction, and ocular dominance maps.

The axonal (bouton) distributions of a layer 4 clutch cell (CC), two layer 3 medium-sized basket cells (MBC), and a layer 3 large basket cell (LBC) to orientation, direction, and ocular dominance maps were studied quantitatively. 1) The CC provided exclusively local projections (<380 microm from the soma) and contacted a narrow "niche" of functional representations. 2) The two MBCs emitted local projections (75% and 79% of all boutons), which were engaged with isoorientations (61% and 48%) and isodirections, and long-range projections (25% and 21%, >313 microm and >418 microm), which encountered cross-orientation sites (14% and 12%) and isoorientation sites (7% and 5%). Their direction preferences were mainly perpendicular to or opposite those of local projections. 3) The LBC provided the majority (60%) of its boutons to long-range distances (>437 microm). Locally, LBC boutons showed a rather balanced contribution to isoorientations (19%) and cross-orientations (12%) and preferred isodirections. Remotely, however, cross-orientation sites were preferred (31% vs. 23%) and the directional output was balanced. 4) Monte Carlo simulations revealed that the differences between the orientation specificity of local and long-range projections cannot be explained by a homogeneous lateral distribution of the boutons. 5) There was a similar eye preference in the local and long-range projection fields of the MBCs. The LBC contacted both contra- and ipsilateral eye domains. 6) The basket axons showed little laminar difference in orientation and direction topography. The results suggest that an individual basket cell can mediate a wide range of effects depending on the size and termination pattern of the axonal field.

Feature selection for DNA methylation based cancer classification.

Molecular portraits, such as mRNA expression or DNA methylation patterns, have been shown to be strongly correlated with phenotypical parameters. These molecular patterns can be revealed routinely on a genomic scale. However, class prediction based on these patterns is an under-determined problem, due to the extreme high dimensionality of the data compared to the usually small number of available samples. This makes a reduction of the data dimensionality necessary. Here we demonstrate how phenotypic classes can be predicted by combining feature selection and discriminant analysis. By comparing several feature selection methods we show that the right dimension reduction strategy is of crucial importance for the classification performance. The techniques are demonstrated by methylation pattern based discrimination between acute lymphoblastic leukemia and acute myeloid leukemia.

Contrast adaptation and infomax in visual cortical neurons.

In the primary visual cortex (V1) the contrast response function of many neurons saturates at high contrast and adapts depending on the visual stimulus. We propose that both effects - contrast saturation and adaptation - can be explained by a fast and a slow component in the synaptic dynamics. In our model the saturation is an effect of fast synaptic depression with a recovery time constant of about 200 ms. Fast synaptic depression leads to a contrast response function with a high gain for only a limited range of contrast values. Furthermore, we propose that slow adaptation of the transmitter release probability at the geniculocortical synapses is the underlying neural mechanism that accounts for contrast adaptation on a time scale of about 7 sec. For the functional role of contrast adaptation we make the hypothesis that it serves to achieve the best visual cortical representation of the geniculate input. This representation should maximize the mutual information between the cortical activity and the geniculocortical input by increasing the release probability in a low contrast environment. We derive an adaptation rule for the transmitter release probability based on this infomax principle. We show that changes in the transmitter release probability may compensate for changes in the variance of the geniculate inputs - an essential requirement for contrast adaptation. Also, we suggest that increasing the release probability in a low contrast environment is beneficial for signal extraction, because neurons remain sensitive only to an increase in the presynaptic activity if it is synchronous and, therefore, likely to be stimulus related. Our hypotheses are tested in numerical simulations of a network of integrate-and-fire neurons for one column of V1 using fast synaptic depression and slow synaptic adaptation. The simulations show that changing the synaptic release probability of the geniculocortical synapses is a better model for contrast adaptation than the adaptation of the synaptic weights: only in the case of changing the transmitter release probability does our model reproduce the experimental finding that the average membrane potential (DC component) adapts much more strongly than the stimulus modulated component (F1 component). In the case of changing the synaptic weights, however, the average membrane potential (DC) as well as the stimulus modulated component (F1 component) would adapt. Furthermore, changing the release probability at the recurrent cortical synapses cannot account for contrast adaptation, but could be responsible for establishing oscillatory activity often observed in recordings from visual cortical cells.

A model for the intracortical origin of orientation preference and tuning in macaque striate cortex.

We report results of numerical simulations for a model of generation of orientation selectivity in macaque striate cortex. In contrast to previous models, where the initial orientation bias is generated by convergent geniculate input to simple cells and subsequently sharpened by lateral circuits, our approach is based on anisotropic intracortical excitatory connections which provide both the initial orientation bias and its subsequent amplification. Our study shows that the emerging response properties are similar to the response properties that are observed experimentally, hence the hypothesis of an intracortical generation of orientation bias is a sensible alternative to the notion of an afferent bias by convergent geniculocortical projection patterns. In contrast to models based on an afferent orientation bias, however, the "intracortical hypothesis" predicts that orientation tuning gradually evolves from an initially nonoriented response and a complete loss of orientation tuning when the recurrent excitation is blocked, but new experiments must be designed to unambiguously decide between both hypotheses.