Specificity and strength of retinogeniculate connections.

Retinal ganglion cells and their target neurons in the principal layers of the lateral geniculate nucleus (LGN) of the thalamus have very similar, center-surround receptive fields. Although some geniculate neurons are dominated by a single retinal afferent, others receive both strong and weak inputs from several retinal afferents. In the present study, experiments were performed in the cat that examined the specificity and strength of monosynaptic connections between retinal ganglion cells and their target neurons. The responses of 205 pairs of retinal ganglion cells and geniculate neurons with overlapping receptive-field centers or surrounds were studied. Receptive fields were mapped quantitatively using a white-noise stimulus; connectivity was assessed by cross-correlating the retinal and geniculate spike trains. Of the 205 pairs, 12 were determined to have monosynaptic connections. Both the likelihood that cells were connected and the strength of connections increased with increasing similarity between retinal and geniculate receptive fields. Connections were never found between cells with <50% spatial overlap between their centers. The results suggest that although geniculate neurons often receive input from several retinal afferents, these multiple afferents represent a select subset of the retinal ganglion cells with overlapping receptive-field centers.

Paired-spike interactions and synaptic efficacy of retinal inputs to the thalamus.

In many neural systems studied in vitro, the timing of afferent impulses affects the strength of postsynaptic potentials. The influence of afferent timing on postsynaptic firing in vivo has received less attention. Here we study the importance of afferent spike timing in vivo by recording simultaneously from ganglion cells in the retina and their targets in the lateral geniculate nucleus of the thalamus. When two spikes from a single ganglion-cell axon arrive within 30 milliseconds of each other, the second spike is much more likely than the first to produce a geniculate spike, an effect we call paired-spike enhancement. Furthermore, simultaneous recordings from a ganglion cell and two thalamic targets indicate that paired-spike enhancement increases the frequency of synchronous thalamic activity. We propose that information encoded in the high firing rate of an individual retinal ganglion cell becomes distributed among several geniculate neurons that fire synchronously. Because synchronous geniculate action potentials are highly effective in driving cortical neurons, it is likely that information encoded by this strategy is transmitted to the next level of processing.

Functional analysis of V3A and related areas in human visual cortex.

Using functional magnetic resonance imaging (fMRI) and cortical unfolding techniques, we analyzed the retinotopy, motion sensitivity, and functional organization of human area V3A. These data were compared with data from additional human cortical visual areas, including V1, V2, V3/VP, V4v, and MT (V5). Human V3A has a retinotopy that is similar to that reported previously in macaque: (1) it has a distinctive, continuous map of the contralateral hemifield immediately anterior to area V3, including a unique retinotopic representation of the upper visual field in superior occipital cortex; (2) in some cases the V3A foveal representation is displaced from and superior to the confluent foveal representations of V1, V2, V3, and VP; and (3) inferred receptive fields are significantly larger in human V3A, compared with those in more posterior areas such as V1. However, in other aspects human V3A appears quite different from its macaque counterpart: human V3A is relatively motion-selective, whereas human V3 is less so. In macaque, the situation is qualitatively reversed: V3 is reported to be prominently motion-selective, whereas V3A is less so. As in human and macaque MT, the contrast sensitivity appears quite high in human areas V3 and V3A.

Representation of motion boundaries in retinotopic human visual cortical areas.

Edges are important in the interpretation of the retinal image. Although luminance edges have been studied extensively, much less is known about how or where the primate visual system detects boundaries defined by differences in surface properties such as texture, motion or binocular disparity. Here we use functional magnetic resonance imaging (fMRI) to localize human visual cortical activity related to the processing of one such higher-order edge type: motion boundaries. We describe a robust fMRI signal that is selective for motion segmentation. This boundary-specific signal is present, and retinotopically organized, within early visual areas, beginning in the primary visual cortex (area V1). Surprisingly, it is largely absent from the motion-selective area MT/V5 and far extrastriate visual areas. Changes in the surface velocity defining the motion boundaries affect the strength of the fMRI signal. In parallel psychophysical experiments, the perceptual salience of the boundaries shows a similar dependence on surface velocity. These results demonstrate that information for segmenting scenes by relative motion is represented as early as V1.

Active p21Ras is sufficient for rescue of NGF-dependent rat sympathetic neurons.

We have examined whether p21Ras proteins can rescue nerve growth factor-deprived rat sympathetic neurons from death, to test further our hypothesis that p21Ras is a central mediator in the nerve growth factor-to-survival signalling pathway. After crosslinking [125I]nerve growth factor to live neurons, two forms of Trk (molecular weight approximately 140,000 and 115,000) were immunoprecipitated with anti-Trk antibodies. Nerve growth factor induced tyrosine phosphorylation of both Trk forms and at least two additional proteins. When these phosphorylations were prevented by staurosporine (in a protein kinase C-independent manner) the neurons died. However, neurons were rescued from death due to staurosporine treatment by intracellular loading of oncogenic Ha-Ras(val12) protein. Both Ha-Ras(val12) and cellular Ha-Ras proteins maintained survival for several days in the absence of nerve growth factor and mimicked other actions of nerve growth factor, inducing rapid c-Fos protein expression and robust neurite outgrowth. Conversely, Fab fragments of neutralizing antibodies to p21Ras which blocked the capacity of nerve growth factor to promote neuron survival were also found to inhibit the early expression of c-Fos protein in these neurons. The close correspondence observed between the timing of onset of c-Fos responsiveness and acquisition of nerve growth factor-dependence in embryonic day 17 sympathetic neurons, and the coordinate increase found in both parameters until embryonic day 19 indicates that c-Fos protein expression is a good biochemical indicator of the presence of a functional nerve growth factor-to-survival signal transduction pathway. Nevertheless, expression of c-Fos is not sufficient for survival since phorbol esters induce c-Fos with no effect on survival. These data strengthen our proposal that p21Ras proteins are crucial anti-apoptotic mediators of survival in rat sympathetic neurons by demonstrating that p21Ras is both necessary and sufficient to rescue neurons which are disabled from signalling through Trk receptors.

Object-related activity revealed by functional magnetic resonance imaging in human occipital cortex.

The stages of integration leading from local feature analysis to object recognition were explored in human visual cortex by using the technique of functional magnetic resonance imaging. Here we report evidence for object-related activation. Such activation was located at the lateral-posterior aspect of the occipital lobe, just abutting the posterior aspect of the motion-sensitive area MT/V5, in a region termed the lateral occipital complex (LO). LO showed preferential activation to images of objects, compared to a wide range of texture patterns. This activation was not caused by a global difference in the Fourier spatial frequency content of objects versus texture images, since object images produced enhanced LO activation compared to textures matched in power spectra but randomized in phase. The preferential activation to objects also could not be explained by different patterns of eye movements: similar levels of activation were observed when subjects fixated on the objects and when they scanned the objects with their eyes. Additional manipulations such as spatial frequency filtering and a 4-fold change in visual size did not affect LO activation. These results suggest that the enhanced responses to objects were not a manifestation of low-level visual processing. A striking demonstration that activity in LO is uniquely correlated to object detectability was produced by the "Lincoln" illusion, in which blurring of objects digitized into large blocks paradoxically increases their recognizability. Such blurring led to significant enhancement of LO activation. Despite the preferential activation to objects, LO did not seem to be involved in the final, "semantic," stages of the recognition process. Thus, objects varying widely in their recognizability (e.g., famous faces, common objects, and unfamiliar three-dimensional abstract sculptures) activated it to a similar degree. These results are thus evidence for an intermediate link in the chain of processing stages leading to object recognition in human visual cortex.

Visual motion aftereffect in human cortical area MT revealed by functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) was used to measure local haemodynamic changes (reflecting electrical activity) in human visual cortex during production of the visual motion aftereffect, also known as the waterfall illusion. As in previous studies, human cortical area MT (V5) responded much better to moving than to stationary visual stimuli. Here we demonstrate a clear increase in activity in MT when subjects viewed a stationary stimulus undergoing illusory motion, following adaptation to stimuli moving in a single local direction. Control stimuli moving in reversing, opposed directions produced neither a perceptual motion aftereffect nor elevated fMRI levels postadaptation. The time course of the motion aftereffect (measured in parallel psychophysical tests) was essentially identical to the time course of the fMRI motion aftereffect. Because the motion aftereffect is direction specific, this indicates that cells in human area MT are also direction specific. In five other retinotopically defined cortical areas, similar motion-specific aftereffects were smaller than those in MT or absent.

Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging.

The borders of human visual areas V1, V2, VP, V3, and V4 were precisely and noninvasively determined. Functional magnetic resonance images were recorded during phase-encoded retinal stimulation. This volume data set was then sampled with a cortical surface reconstruction, making it possible to calculate the local visual field sign (mirror image versus non-mirror image representation). This method automatically and objectively outlines area borders because adjacent areas often have the opposite field sign. Cortical magnification factor curves for striate and extrastriate cortical areas were determined, which showed that human visual areas have a greater emphasis on the center-of-gaze than their counterparts in monkeys. Retinotopically organized visual areas in humans extend anteriorly to overlap several areas previously shown to be activated by written words.

Functional analysis of human MT and related visual cortical areas using magnetic resonance imaging.

Using noninvasive functional magnetic resonance imaging (fMRI) technique, we analyzed the responses in human area MT with regard to visual motion, color, and luminance contrast sensitivity, and retinotopy. As in previous PET studies, we found that area MT responded selectively to moving (compared to stationary) stimuli. The location of human MT in the present fMRI results is consistent with that of MT in earlier PET and anatomical studies. In addition we found that area MT has a much higher contrast sensitivity than that in several other areas, including primary visual cortex (V1). Functional MRI half-amplitudes in V1 and MT occurred at approximately 15% and 1% luminance contrast, respectively. High sensitivity to contrast and motion in MT have been closely associated with magnocellular stream specialization in nonhuman primates. Human psychophysics indicates that visual motion appears to diminish when moving color-varying stimuli are equated in luminance. Electrophysiological results from macaque MT suggest that the human percept could be due to decreases in firing of area MT cells at equiluminance. We show here that fMRI activity in human MT does in fact decrease at and near individually measured equiluminance. Tests with visuotopically restricted stimuli in each hemifield produced spatial variations in fMRI activity consistent with retinotopy in human homologs of macaque areas V1, V2, V3, and VP. Such activity in area MT appeared much less retinotopic, as in macaque. However, it was possible to measure the interhemispheric spread of fMRI activity in human MT (half amplitude activation across the vertical meridian = approximately 15 degrees).