Topography of contextual modulations mediated by short-range interactions in primary visual cortex.

Neurons in primary visual cortex (V1) respond differently to a simple visual element presented in isolation from when it is embedded within a complex image. This difference, a specific modulation by surrounding elements in the image, is mediated by short- and long-range connections within V1 and by feedback from other areas. Here we study the role of short-range connections in this process, and relate it to the layout of local inhomogeneities in the cortical maps of orientation and space. By measuring correlation between neuron pairs located in optically imaged maps of V1 orientation columns we show that the strength of local connections between cells is a graded function of lateral separation across cortex, largely radially symmetrical and relatively independent of orientation preferences. We then show the contextual influence of flanking visual elements on neuronal responses varies systematically with a neuron's position within the cortical orientation map. The strength of this contextual influence on a neuron can be predicted from a model of local connections based on simple overlap with particular features of the orientation map. This indicates that local intracortical circuitry could endow neurons with a graded specialization for processing angular visual features such as corners and T junctions, and this specialization could have its own functional cortical map, linked with the orientation map.     

Detection in vivo of protein-DNA interactions within the lac operon of Escherichia coli

Studies of the sequence-specific binding of proteins to DNA have so far relied on in vitro experiments using cloned restriction fragments containing the relevant DNA sequences. We have applied the genomic sequencing technique of Church and Gilbert to show that the interactions observed in vitro occur in vivo. We use this approach to study the binding of regulatory proteins to the lac operon in vivo and detect changes in the reactivity (inhibition or enhancement) of guanines to methylation by dimethyl sulphate caused by the proximity of proteins to the N-7 atom of these guanines. We can detect the simultaneous binding of the catobolite gene activator protein (CAP) and the Lac repressor to their specific recognition sequences, and following induction of the lac operon we observe effects that are related to RNA polymerase binding or RNA elongation. We have successfully used oligonucleotide probes as short as 17 bases to display genomic sequence.     

Translocation of vesicles from squid axoplasm on flagellar microtubules

Directed intracellular particle movement is a fundamental process characteristic of all cells. During fast axonal transport, membranous organelles move at rapid rates, from 1 to 5 micron s-1, in either the orthograde or retrograde direction along the neurone and can traverse distances as long as 1 m (for reviews, see refs 1-3). Recent studies indicate that this extreme example of intracellular motility can occur along single microtubules, but the molecules generating the motile force have not been identified or localized. It is not known whether the force-transducing 'motor' is associated with the moving particle or with the microtubule lattice. To distinguish between these hypotheses and to characterize the membrane-cytoskeletal interactions that occur during vesicle translocations, we have developed a reconstituted model for microtubule-based motility. We isolated axoplasmic vesicles from the giant axon of the squid Loligo pealei as described previously. The vesicles (35-475 nm in diameter) were then added to axonemes of Arbacia punctulata spermatozoa that served as a source of microtubules. Axonemes were used because the tubulin subunit lattice of the A-subfibre of a given outer doublet is the same as the subunit lattice of neuronal microtubules along which motility occurs. Moreover, all the microtubules of a single axoneme show the same structural polarity, indicating that the axoneme represents an oriented microtubule substrate. Here we demonstrate that vesicle motility is ATP-dependent, that it is not mediated by the flagellar force-transducing molecule dynein and that the direction of movement is not specified by microtubule polarity.     

Combining var estimation and state space model reduction for simple good predictions

A combination of VAR estimation and state space model reduction techniques are examined by Monte Carlo methods in order to find good, simple to use, procedures for determining models which have reasonable prediction properties. The presentation is largely graphical. This helps focus attention on the aspects of the model determination problem which are relatively important for forecasting. One surprising result is that, for prediction purposes, knowledge of the true structure of the model generating the data is not particularly useful unless parameter values are also known. This is because the difficulty in estimating parameters of the true model causes more prediction error than results from a more parsimonious approximate model.     

Functional architecture of cortex revealed by optical imaging of intrinsic signals

Optical imaging of cortical activity offers several advantages over conventional electrophysiological and anatomical techniques. One can map a relatively large region, obtain successive maps to different stimuli in the same cortical area and follow variations in response over time. In the intact mammalian brain this imaging has been accomplished with the aid of voltage sensitive dyes. However, it has been known for many years that some intrinsic changes in the optical properties of the tissue are dependent on electrical or metabolic activity. Here we show that these changes can be used to study the functional architecture of cortex. Optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex, obtained by reflection measurements of the intrinsic signal, were confirmed with voltage sensitive dyes or by electrophysiological recordings. In addition, we describe an intrinsic signal originating from small arteries which can be used to investigate the communication between local neuronal activity and the microvasculature. One advantage of the method is that it is non-invasive and does not require dyes, a clear benefit for clinical applications.     

The effects of cocaine in the production of cardiovascular anomalies inβ-Adrenoreceptor stimulated chick embryos

Summary Cocaine potentiates the effects of epinephrine and norepinephrine in terms of aortic arch malformation in embryonic chicks. Cocaine itself induces aortic arch malformations when administered in large doses.This study was supported by grant No. HL 18050, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland.     

Aspartate and glutamate as possible neurotransmitters of cells in layer 6 of the visual cortex

Earlier work has suggested that aspartate, glutamate and gamma-aminobutyric acid (GABA) act as transmitters in the cerebral cortex. There is reasonable evidence for the identity of the cell population responsible for GABA release but until now there has been little evidence concerning the sources for release of aspartate and glutamate. Here we have used two approaches to identify possible neurotransmitters used by cells in the visual cortex: measurement of the efflux of endogenous compounds in conditions of synaptic release and localization of these compounds to particular cell classes using neurotransmitter-specific histochemical techniques. Our results suggest that the acidic amino acids aspartate and glutamate may be cortical neurotransmitters, as shown by calcium-dependent release from endogenous stores and by uptake specific to pyramidal cells in layer 6 of the cortex. These substances may therefore have a role in the function of layer 6 cells, which are responsible for the recurrent projection from the cortex to the lateral geniculate nucleus and for the projection within the cortex from layer 6 to layer 4.