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Key Points Fixational eye movements are small displacements of the eyeballs which ensure that vision does not fade during fixation. There are three classes — tremor (the smallest), drifts and microsaccades (the largest). Traditionally, fixational eye movements have been studied with retinal stabilization techniques. The functional role of fixational eye movements in perception is controversial. Microsaccades have received the most attention, and there is evidence for and against their role in perception. However, the existence of microsaccade-related activity in the visual pathway indicates that they might be involved in perception. Several studies have focused on unravelling the neural code of the responses elicited by the different fixational eye movements. Microsaccades have been most extensively studied. The burst-like nature of the activity elicited by microsaccades has attracted particular attention, but its physiological meaning remains uncertain. Despite the existence of fixational eye movements, perception is stable. This fact has been explained by a hypothetical microsaccadic suppression mechanism, and several models for such a mechanism have been proposed. The underlying phenomena have yet to be discovered. Fixational eye movements can be modulated by environmental (illumination conditions) and cognitive (attention) factors. Other phenomena also seem to exert a modulatory influence on these movements, but such factors need to be investigated. Among the outstanding questions in this field are: which circuits control fixational eye movements; what is the neural basis of microsaccadic suppression; what are the mechanisms that underlie the effect of cognitive factors during fixation; and what is the meaning of the burst firing that is correlated with microsaccades? Our eyes continually move even while we fix our gaze on an object. Although these fixational eye movements have a magnitude that should make them visible to us, we are unaware of them. If fixational eye movements are counteracted, our visual perception fades completely as a result of neural adaptation. So, our visual system has a built-in paradox — we must fix our gaze to inspect the minute details of our world, but if we were to fixate perfectly, the entire world would fade from view. Owing to their role in counteracting adaptation, fixational eye movements have been studied to elucidate how the brain makes our environment visible. Moreover, because we are not aware of these eye movements, they have been studied to understand the underpinnings of visual awareness. Recent studies of fixational eye movements have focused on determining how visible perception is encoded by neurons in various visual areas of the brain.

When images are stabilized on the retina, visual perception fades. During voluntary visual fixation, however, constantly occurring small eye movements, including microsaccades, prevent this fading. We previously showed that microsaccades generated bursty firing in the primary visual cortex (area V-1) in the presence of stationary stimuli. Here we examine the neural activity generated by microsaccades in the lateral geniculate nucleus (LGN), and in the area V-1 of the awake monkey, for various functionally relevant stimulus parameters. During visual fixation, microsaccades drove LGN neurons by moving their receptive fields across a stationary stimulus, offering a likely explanation of how microsaccades block fading during normal fixation. Bursts of spikes in the LGN and area V-1 were associated more closely than lone spikes with preceding microsaccades, suggesting that bursts are more reliable than are lone spikes as neural signals for visibility. In area V-1, microsaccade-generated activity, and the number of spikes per burst, was maximal when the bar stimulus centered over a receptive field matched the cell's optimal orientation. This suggested burst size as a neural code for stimuli optimality (and not solely stimuli visibility). As expected, burst size did not vary with stimulus orientation in the LGN. To address the effectiveness of microsaccades in generating neural activity, we compared activity correlated with microsaccades to activity correlated with flashing bars. Onset responses to flashes were about 7 times larger than the responses to the same stimulus moved across the cells' receptive fields by microsaccades, perhaps because of the relative abruptness of flashes.

When viewing a stationary object, we unconsciously make small, involuntary eye movements or ‘microsaccades’. If displacements of the retinal image are prevented, the image quickly fades from perception. To understand how microsaccades sustain perception, we studied their relationship to the firing of cells in primary visual cortex (V1). We tracked eye movements and recorded from V1 cells as macaque monkeys fixated. When an optimally oriented line was centered over a cell's receptive field, activity increased after microsaccades. Moreover, microsaccades were better correlated with bursts of spikes than with either single spikes or instantaneous firing rate. These findings may help explain maintenance of perception during normal visual fixation.

Scientists' understanding of two central problems in neuroscience, psychology, and philosophy has been greatly influenced by the work of David Hubel and Torsten Wiesel: What is it to see? This relates to the machinery that underlies visual perception, How do we acquire the brain's mechanisms for vision? This is the nature-nurture question as to whether the nerve connections responsible for vision are innate or whether they develop through experience in the early life of an animal or human. This is a book about the collaboration between Hubel and Wiesel, which began in 1958, lasted until about 1982, and led to a Nobel Prize in 1981. It opens with short biographies of both men, describes the state of the field when they started, and talks about the beginnings of their collaboration. It emphasizes the importance of various mentors in their lives, especially Stephen W. Kuffler, who opened up the field by studying the cat retina in 1950, and founded the department of neurobiology at Harvard Medical School, where most of their work was done. The main part of the book consists of Hubel and Wiesel's most important publications. Each reprinted paper is preceded by a foreword that tells how they went about the research, what the difficulties and the pleasures were, and whether they felt a paper was important and why. Each is also followed by an afterword describing how the paper was received and what developments have occurred since its publication. The reader learns things that are often absent from typical scientific publications, including whether the work was difficult, fun, personally rewarding, exhilarating, or just plain tedious. The book ends with a summing-up of the present state of the field.

On testing my own vision in very dim light I observed two phenomena associated with the lack of retinal rods (the receptors specialized for vision in dim light) in the fovea, the region corresponding to our centre of gaze. First, a bright (or dark) straight line passing through the fovea was seen as discontinuous, with a clear 1° gap. Second, after adapting to dim light conditions, when I blocked light to one eye as far as possible and viewed a brightly lit surface with the other eye, I perceived a swarm of colourless scintillations throughout the visual field of the occluded eye, except for an area about 1° in diameter at the centre of gaze. Each scintillation may represent the simultaneous capture of single quanta by several closely spaced rods.

Neurons in macaque primary visual cortex are spatially arranged by their global topographic position and in at least three overlapping local modular systems: ocular dominance columns, orientation pinwheels, and cytochrome oxidase (CO) blobs. Individual neurons in the blobs are not tuned to orientation, and populations of neurons in the pinwheel center regions show weak orientation tuning, suggesting a close relation between pinwheel centers and CO blobs. However, this hypothesis has been challenged by a series of optical recording experiments. In this report, we show that the statistical error associated with photon scatter and absorption in brain tissue combined with the blurring introduced by the optics of the imaging system has typically been in the range of 250 μm. These physical limitations cause a systematic error in the location of pinwheel centers because of the vectorial nature of these patterns, such that the apparent location of a pinwheel center measured by optical recording is never (on average) in the correct in vivo location. The systematic positional offset is ≈116 μm, which is large enough to account for the claimed misalignment of CO blobs and pinwheel centers. Thus, optical recording, as it has been used to date, has insufficient spatial resolution to accurately locate pinwheel centers. The earlier hypothesis that CO blobs and pinwheel centers are coterminous remains the only hypothesis currently supported by reliable observation.

In the retina, dopamine plays a central role in neural adaptation to light. Progress in the study of dopaminergic amacrine (DA) cells has been limited because they are very few (450 in each mouse retina, 0.005% of retinal neurons). Here, we applied transgenic technology, single-cell global mRNA amplification, and cDNA microarray screening to identify transcripts present in DA cells. To profile gene expression in single neurons, we developed a method (SMART7) that combines a PCR-based initital step (switching mechanism at the 5′ end of the RNA transcript or SMART) with T7 RNA polymerase amplification. Single-cell targets were synthesized from genetically labeled DA cells to screen the RIKEN 19k mouse cDNA microarrays. Seven hundred ninety-five transcripts were identified in DA cells at a high level of confidence, and expression of the most interesting genes was confirmed by immunocytochemistry. Twenty-one previously undescribed proteins were found in DA cells, including a chloride channel, receptors and other membrane glycoproteins, kinases, transcription factors, and secreted neuroactive molecules. Thirty-eight percent of transcripts were ESTs or coding for hypothetical proteins, suggesting that a large portion of the DA cell proteome is still uncharacterized. Because cryptochrome-1 mRNA was found in DA cells, immunocyto-chemistry was extended to other components of the circadian clock machinery. This analysis showed that DA cells contain the most common clock-related proteins.

When we talk about animal research, the case of researching primates is the extreme one. To experiment with such magnificent creatures requires corresponding justification. Many human diseases occur in other primates but not in other animals. Primates are particularly important in medical research because they are genetically closest to humans. Their brains most closely resemble the human brain. It would not have been possible to develop and test the polio vaccine without using primates.

In the course of examining single unit responses from the cortex of unrestrained and unanesthetized cats, we have come upon a population of cells that appears to be sensitive to auditory stimuli only if the cat \"pays attention\" to the sound source. We have described these responses, since they have not been previously reported and since they illustrate an important difference between the information which can be gleaned from experiments of this type and that obtained in the usual \"acute\" microelectrode experiment.

Vernier acuity is a measure of the smallest horizontal offset between two vertical lines that can be behaviorally discriminated. To examine the link between the neuronal responses in a retinotopic mosaic and vernier acuity, we recorded the responses of single cells in cat lateral geniculate nucleus to a vertical bar stimulus that was stepped in small increments through the receptive fields of cells. Based on the single-trial responses evoked by stimuli at different positions, we calculated the spatial resolution that could be achieved. If the stimulus could fall anywhere in their receptive fields, single neurons had spatial resolutions two times worse than previously reported vernier thresholds. Given the known coverage factor in a cat retina, we developed a two-stage decision model to examine how the responses of neurons in a retinotopic mosaic could be processed to achieve vernier acuity. In order for psychophysical thresholds to be accounted for by the responses of a single cell, the stimulus must fall in the quarter of the receptive field that provides the most information about stimulus position. Alternatively, both the absolute psychophysical threshold for vernier acuity and its dependence on stimulus length can be realized by pooling the responses of a few neurons, all located on one side of the bar stimulus.