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Young sensory systems often utilize stimuli present in the environment during development to refine information processing. These processes work to optimize the system for the encoding of future sensory stimuli. The seminal observations of David Hubel and Torsten Wiesel in the 1960s demonstrated the detrimental effects of sensory deprivation on the development of the mammalian visual system (Hubel and Wiesel 1965, 1970). When reared under conditions of monocular deprivation, the development of eye-specific columns in the visual cortex is severely disrupted such that, despite the fact that it retains a fully functional eye, the animal is unable to properly encode information originating from the deprived eye. Such is the case in children born with strabismus (lazy eye or squint). If left without treatment during youth, strabismic children suffer severe visual deficits as adults.

Although it is generally agreed that neural activity plays an important role in the proper development of the visual system, the mechanisms by which this occurs and the extent to which activity can instruct visual development remains hotly debated. We have investigated these questions using the visual system of the developing Xenopus laevis tadpole. In frogs and fish, the optic tectum receives direct excitatory input from the contralateral retina (the retinotectal projection). Each neuron in the optic tectum has a receptive field (RF), which is composed of inputs from the retina that are activated by stimuli presented in a particular region of visual space. These inputs have been shown to undergo spike-timing dependent plasticity (STDP)—a mechanism whereby the timing between presynaptic (retina) and postsynaptic (tectum) activity determines the direction of synaptic strength modifications (Zhang et al. 1998). When the postsynaptic cell is active within 20 milliseconds after receiving a presynaptic input, this input becomes strengthened. Conversely, if the postsynaptic cell is active prior to receiving an input, this synapse becomes weakened.

By directing STDP to a subset of visual inputs comprising the periphery of the RF, we were able to show that positive STDP training—presynaptic before postsynaptic activity—causes a shift in RF position towards the trained region of visual space. When the timing of the visual stimulus was reversed—presynaptic after postsynaptic activity—the RF reliably moved away from this region of visual space. Unexpectedly, the modification of the responses to stimuli from a certain region of visual space also induces indirect changes in other inputs, suggesting a heterosynaptic spread of potentiation. Additionally, the induced RF and synaptic modification were subject to reversal by subsequent postsynaptic spiking, highlighting the vulnerable nature of such induced changes. Taken together, these results posit an instructive role for activity in the development of the visual system and uncover potential functions for heterosynaptic plasticity in sensory representation refinement.

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Reference List

Hubel, D. H. and Wiesel, T. N. (1965). Binocular interaction in striate cortex of kittens reared with artificial squint. J.Neurophysiol.28:1041–1059.

Hubel, D. H. and Wiesel, T. N. (1970). The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J.Physiol. 206:419–436.

Zhang, L. I., Tao, H. W., Holt, C. E., Harris, W. A., and Poo, M. (1998). A critical window for cooperation and competition among developing retinotectal synapses. Nature 395:37–44.

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(l to r) Florian Engert, Adam R. Kampff and Rebecca L. Vislay-Meltzer

(l to r) Florian Engert, Adam R. Kampff and Rebecca L. Vislay-Meltzer