The pioneering experiments performed by Hubel and Weisel in the late 1950s and early 60s taught us much about the development of the visual system. We now know, for example, that neurons in the visual cortex are organized into alternating ocular dominance columns which receive inputs from either the left or right eye and that groups of cells within these columns respond selectively to bars or edges of a specific orientation moving in a specific direction.
Hubel and Weisel also found that the proper development of these areas of the brain is dependent upon visual information from the eyes. Their work showed that the visual cortex fails to develop properly if deprived of sensory input during a specific time window. This firmly established the idea of the “critical period”, and immediately suggested treatments for young children with eye conditions such as amblyopia (“lazy eye”) and strabismus (“crossed eyes”).
Now researchers from Duke University Medical Center have observed how early visual experience drives maturation of the visual cortex. Using sophisticated in vivo imaging techniques, they have monitored the changes in the functional properties of visual cortical neurons which occur immediately following eye opening in ferrets. In this way, they show how the first stimuli to enter the eye lead to the emergence of direction selectivity in visually naïve neurons and to the organization of the cells into groups which respond to a preferred direction.
By the time a ferret is born, its brain contains more neurons than are needed. The cells have sprouted axons and dendrites, and have formed functional connections with each other, as a result of spontaneous electrical activity. Neurons in the primary visual cortex are already organized into ocular dominance columns, which give that part of the brain its characteristic striped appearance. At the time of birth, connectivity within the visual cortex is extensive and exuberant – many redundant connections have formed, and they will be pruned only when the eyes open to allow visual information to flow in. Likewise, neuronal activity bears little relation to goings-on in the outside world, and only with experience is it tuned to environmental stimuli.
For their experiments, David Fitzpatrick and his colleagues placed anaesthetized ferrets into a sterotaxic head frame and removed small pieces of bone from the part of the skull lying above the primary visual cortex. After injecting a calcium-sensitive dye into the visual cortex, they mounted a small steel chamber onto the skull, attached it firmly to the edges of the craniotomy with dental acrylic, and sealed it with a glass coverslip. Using two-photon laser scanning microscopy to measure changes in calcium ion concentration, the researchers observed the activity of visual cortical neurons in the live animals in response to early visual stimulation.
Fitzpatrick’s group monitored the activity of hundreds of individual neurons, at depths of between 120 and 300 thousandths of a millimeter beneath the cortical surface. The 1-month-old animals had just opened their eyes and so had been exposed to less than 1 day of visual experience. In line with earlier findings, the primary visual cortex of these visually naive already contained well-defined groups of neurons which responded selectively to stimuli of a prefered orientation. However, the cells did not exhibit any preference for direction of movement, a property which is known to develop at around 7 days after opening of the eyes.
Plots of direction preference of neurons in the primary visual cortex of visually naïve (left) and experienced (right) juvenile ferrets. Each cell is represented by an arrow, with size and length of the arrow indicating the magnitude of the response. The colours denote cells with opposite orientation preferences. (From Li et al, 2008)
In order to determine whether moving visual stimuli were sufficient to induce the emergence of direction-selective responses, the animals were exposed to two “training” stimuli consisting of grating patterns which drifted back and forth across the visual field perpendicular to the orientation of the grating in opposite directions. These stimuli were presented to the ferrets for 5 seconds at a time, with intervals of 10 seconds, for a period of 20 minutes. Subsequently, the activity of primary visual cortical neurons was observed whilst these stimuli were presented again.
For the first 8-10 hours of visual stimulation after this motion training, no changes were observed in the functional properties of visual cortical neurons. Most neurons were highly responsive to the orientation of the stimuli, but their selectivity to the direction in which the stimuli moved was very weak. Later on, small groups of cells with a preference for one of the two training stimuli began to emerge. With time, these responses progressively increased, so that each group became highly tuned to one or the other training stimuli (see above figure). The number of neurons selective for each orientation was also found to increase with time.
To test whether it was the motion of the training stimuli that induced these changes in activity, the researchers flashed identical gratings in the ferrets’ visual fields for brief periods of time. This “flash training” elicited responses in the same cortical neurons, but the responses did not increase with time. Gratings which moved in eight directions that differed from those in the training elicited little response or none at all. This confirmed that the observed emergence of orientation selectivity was indeed due to exposure to the training stimuli.
Closer examination of the responses of individual pyramidal neurons in layer 2/3 of the cortex revealed that the preferred direction of motion of each changed over time, so that it became more like the preferences of its neighbours. Prior to training, most of the cells exhibited uncertain or moderate orientation preferences. Upon presentation of the training stimuli, however, the responses of most neurons became more certain, and the neurons segregated into small domains with a preference for one direction or the other.
Other interesting functional changes were also observed. Some neurons maintained their initial moderate preference for one direction of movement and later increased their response to it, while others reversed their orientation preference during training. If, for example, a neuron was surrounded by cells with a preference for the opposite direction, it was likely to reverse its own preference so that it matched that of its neighbours. On the other hand, a neuron surrounded by others with the same preference was unlikely to change its own preference during training. This suggests that the functinal grouping of neurons occurs because of some kind of interaction between neighbouring cells during motion training.
These experiments show that early experience of moving visual stimuli has a strong and relatively rapid effect on the functional properties of neurons in the primary visual cortex. Initially, the ferret primary visual cortex contains an array of neurons with weak direction preferences, possibly because of light entering through the closed eye lids. The two training stimuli used, which consisted of gratings moving in opposite directions, transformed this array into two highly ordered columns, each containing neurons with a highly selective preference for one of the directions of stimulus motion. The study supports the widely-held belief that sensory experience is essential for proper visual development, but adds some fascinating details of how it does so. It also raises the question of exactly how visual cortical neurons interact with each other during their selection of direction preference.
Li, Y. et al (2008). Experience with moving visual stimuli drives the early development of cortical direction selectivity. Nature. DOI: 10.1038/nature07417