6
Visual development:
an activity-dependent process
Variations on a theme
The development of the visual system is under the control of both genetic and environmental factors. The connections are refined and cut to fit on the basis of neural activity that is constantly flickering through the visual system from the retina. Following birth, it is environmental stimulation that elicits neural activity in the visual system. Cells in the retina, LGN and V1 of newborn, visually naı¨ve monkeys and kittens have receptive field and response properties very much like those of the adults. However, there are differences in their visual systems, such as in layer 4 of V1 where the projections from the LGN terminate. At birth, the cells in layer 4 are driven by both eyes, as projections from the LGN spread over a wide region of layer 4, whereas in the adult a layer 4 cell is driven by either eye but not by both. The adult pattern of ocular dominance columns in layer 4 is established over the first 6 weeks of life, when the LGN axons retract to establish separate, alternating zones in layer 4 that are supplied exclusively by one eye or the other (Figure 6.1).
In early life, the connections of neurons in the visual system are susceptible to change and can be affected irreversibly by unbalanced neural activity passing through them. For example, closure of the lids of one eye during the first 3 months of life leads to blindness in that eye. This is not because the eye no longer functions properly, but because the neurons in the visual cortex no longer respond to the signals the eye sends to them. Lid closure in adult animals has no such effect. It seems that, for the visual system to be correctly wired up, it must receive stimulation from the eyes to guide its development and allow connections to be strengthened or weakened, depending on the activity in the system. The most favoured theory for the mechanism underlying neural plasticity in adult animals was proposed back in the 1940s by Hebb. He suggested a coincidence detection rule such that, when two cells are simultaneously active, the synapse connecting them is strengthened (Hebb, 1949) (see
90 V I S U A L D E V E L O P M E N T
Figure 6:1: A schematic representation of the retraction of cat LGN axons which terminate on layer 4 of the visual cortex during the first six weeks of life. The overlap of the inputs from the right
(R) and left (L) eye present at birth gradually become segregated into separate clusters corresponding to the ocular dominance columns (redrawn from Nicholls, Martin & Wallace, 1992).
Figure 6:2: A schematic diagram of four inputs synapsing onto a neuron. Inputs 1 and 2 fire simultaneous bursts of action potentials, which results in the strong depolarisation of the postsynaptic cell. Inputs 3 and 4 are not firing in synchrony, and so produce only a weak post-synaptic depolarisation. The coincident preand post-synaptic activity strengthens inputs 1 and 2, and weakens that of 3 and 4 (redrawn
from Weliky, 2000).
Figure 6.2). The discovery of a putative cellular substrate for learning long-term potentiation (LTP) by Lomo in 1966 has resulted in a veritable deluge of studies. This work has been centred very largely on the hippocampus, an important area for learning and memory. In the hippocampus, LTP is characterised by an abrupt and sustained increase in the efficiency of synaptic transmission brought on by a brief high frequency stimulus. It may persist in the in vitro hippocampal slice for hours and in a freely moving animal for days (Bliss & Collingridge, 1993).
Although LTP does seem to be the most likely candidate for the mechanism of activity-dependent synaptic plasticity, it continues to be extraordinarily difficult to determine exactly how this synapse strengthening comes about. One generally agreed feature is that N-methyl-D-aspartate (NMDA) receptors, a sub-type of glutamate receptor, mediate the entry of Ca2 þ in CA1 of the hippocampus and thus induce LTP, although NMDA receptors are not necessarily involved in LTP at other sites. The NMDA receptors open in the presence of L-glutamate when the post-synaptic membrane is depolarised
M O N OC U L A R O R B I N O C U L A R D E P R I V A T I O N 91
sufficiently to expel the channel blocker Mg2 þ. Much of the current debate concerns the site that controls LTP expression: is it presynaptic or postsynaptic? Is control dependent on the specific experimental condition? In spite of this continuing tussle, the evidence for LTP as a general model of synaptic plasticity in the adult brain is increasing. But, what of the plasticity involved in the developing brain – is there a common mechanism? This chapter will examine the evidence for changes in the visual system with changes in visual input, and the possible mechanisms that might mediate these changes.
Monocular or binocular deprivation
The segregation of the LGN axons to form ocular dominance columns seems to be dependent on balanced activity from the two eyes. If this activity is interrupted and the balance between the two eyes is altered, then the result is a series of changes in the organisation of the visual system. One rather drastic way of altering the balance of activity is to close one eye in a developing animal. Rearing kittens with one eye sutured (monocular deprivation) causes a series of changes throughout the visual system and drastically reduces the perceptual capabilities of the eye that has been sutured during the early development. In the LGN, neurons connected to the deprived eye were reduced in size by 40% relative to the neurons connected to the other eye (Wiesel & Hubel, 1963). Further studies on the terminal fields of the LGN cells in layer 4 showed that LGN axons connected to the deprived eye occupied less than 20% of the cortical area, and the other non-deprived eye had expanded its representation to cover more that 80% of the thalamic recipient zone (LeVay, Stryker & Shatz, 1978). Single unit recording studies have shown that stimuli presented through the formerly deprived eye failed to influence the majority of cells in the striate visual cortex (Figure 6.3). The undeprived eye becomes the primary effective route for visual stimuli.
Under conditions of dark rearing (binocular deprivation), the organisation of the visual system and the selectivity of the cells initially continue to develop, despite the lack of visual stimuli (Buisseret & Imbert, 1976). When both eyes are closed in newborn monkeys for 17 days or longer, most cortical cells (such as the simple and complex cells) respond largely as normal to visual stimuli (Daw et al., 1983). The organisation of layer 4 seems to be normal and in other layers most cortical cells are stimulated by both eyes. The major difference is that a large proportion of cells could not be driven at all, while others were less tightly tuned to stimulus orientation. Binocular deprivation in kittens leads to similar results except that more cortical cells continue to be binocularly driven (Wiesel & Hubel, 1965). Longer visual deprivation (3 months or more) leads to a more marked effect. The visual cells become weakly responsive or totally unresponsive to visual stimuli, and the weakly responding cells lack
92 V I S U A L D E V E L O P M E N T
Figure 6:3: Ocular dominance histograms in cells recorded from V1 in cats. (a) Recordings for 223 cells of adult cats. Cells in groups 1 and 7 of the histogram are driven by one eye only (ipsilateral or contralateral). All the other cells have inputs from both eyes. In groups 2, 3, 5 and 6, the input from one eye is dominant. In group 4, both eyes have a roughly equal influence. (b) Recordings from
25 cells of a kitten that was reared with its right eye occluded until the time of the experiment. The dashed bar on the right indicates that five cells did not respond to the stimulation of either eye. The solid bar indicates that all 20 cells that were responsive to stimulation responded only to the eye that was opened during rearing (redrawn from Wiesel & Hubel, 1963).
orientation, direction and stereo selectivity (Sherk & Stryker, 1976; Pettigrew, 1974). It seems that some of the results of monocular deprivation can be prevented or reduced by binocular deprivation. It may be that the two eyes are competing for representation in the cortex and, with one eye closed, the contest becomes unequal.
What, then, is the physiological basis for this ocular dominance shift associated with monocular deprivation? Such a shift can be prevented by modifying neuromodulator and neurotransmitter functions in the cortex (e.g. Shaw & Cynader, 1984; Bear & Singer, 1986; Reiter & Stryker, 1988), for example, by the infusion of glutamate into the cortex for a 2-week period during monocular deprivation. Control recordings during the infusion period show that cortical neurons in general fail to respond well to visual stimuli from either eye during the infusion period. The lack of ocular dominance modification seems to be the result of the reduced ability of the cortical cells to respond to the unbalanced LGN afferent input. Effective inputs representing the two eyes are greater than that of the deprived