Aminoaciduria in pernicious anaemia.

Abstract

Neural circuits are shaped by experience during critical periods of development. Sensory deprivation during these periods permanently compromises an organism9s ability to perceive the outside world. In the mouse visual system, normal visual experience during a critical period in early life drives the matching of individual cortical neurons9 orientation preferences through the two eyes, likely a key step in the development of binocular vision. Here, in mice of both sexes, we show that the binocular matching process is completely blocked by monocular deprivation spanning the entire critical period. We then show that three weeks of environmental enrichment (EE), a paradigm of enhanced sensory, motor and cognitive stimulation, is sufficient to rescue binocular matching to the level seen in un-manipulated mice. In contrast, six weeks of conventional housing only resulted in a partial rescue. Finally, we use two-photon calcium imaging to track the matching process chronically in individual cells during EE-induced rescue. We find that for cells which are clearly dominated by one of the two eyes, the input representing the weaker eye changes its orientation preference to align with that of the dominant eye. These results thus reveal ocular dominance as a key driver of the binocular matching process, and suggest a model whereby the dominant input instructs the development of the weaker input. Such a mechanism may operate in the development of other systems that need to integrate inputs from multiple sources in order to generate normal neuronal functions. <b>SIGNIFICANCE STATEMENT</b> Critical periods are developmental windows of opportunity that ensure the proper wiring of neural circuits, as well as windows of vulnerability when abnormal experience could cause lasting damage to the developing brain. In the visual system, critical period plasticity drives the establishment of binocularly-matched orientation preferences in cortical neurons. Here, we show that binocular matching is completely blocked by monocular deprivation during the critical period. Moreover, environmental enrichment can fully rescue the disrupted matching, whereas conventional housing of twice the duration results in a partial rescue. We then use two-photon calcium imaging to track individual cells chronically during the EE-induced recovery, and reveal important insights into how appropriate function can be restored to the nervous system after the critical period.