The Impact of Brief Monocular Retinal Inactivation on the Central Visual System During Postnatal Development

Abstract

During a critical period of postnatal life, monocular deprivation (MD) of kittens by eyelid closure reduces the size of neurons in layers of the dorsal lateral geniculate nucleus (dLGN) connected to the deprived eye, and shifts cortical ocular dominance in favor of the non-deprived eye, modeling deprivation amblyopia in humans. Following long-term MD, temporary retinal inactivation of the non-deprived eye with microinjection of tetrodotoxin can promote superior recovery from MD, and at older ages, in comparison to conventional occlusion therapy. This suggests that monocular inactivation (MI) is a more potent approach to producing neural plasticity than occlusion. In the current study we assessed the modification of neuron size in the dLGN as a means of measuring the impact of a brief period of MI imposed at different ages during postnatal development. The biggest impact of inactivation was observed when it occurred at the peak of the critical period for ocular dominance plasticity. The effect of MI was evident in both the binocular and monocular segments of the dLGN, distinguishing it from MD that produces changes only within the binocular segment. With increasing age, the capacity for inactivation to alter postsynaptic cell size diminished but was still significant beyond the classic critical period. In comparison to MD, inactivation consistently produced effects that were about double in magnitude, and inactivation exhibited efficacy to produce neural modifications at older ages than MD. Notwithstanding the large neural alterations precipitated by inactivation, its anatomical effects were remediated with a short period of binocular visual experience, and vision through the previously inactivated eye fully recovered after washout of TTX. Our results demonstrate that MI is a potent means of modifying the visual pathway, and does so beyond the age at which occlusion is effective. The magnitude and longevity of inactivation to evoke neural modification highlights its potential to ameliorate disorders of the visual system such as amblyopia.