Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision

Abstract

The maturation of inhibitory circuits in the juvenile cortex triggers a critical period of plasticity in visual system development. Although several manipulations of inhibition can alter its timing, none have reactivated critical period plasticity in adulthood. We developed a transplantation method to reactivate critical period plasticity in the adult visual cortex. Transplanted embryonic inhibitory neurons from the medial ganglionic eminence reinstate ocular dominance plasticity in adult recipients. Transplanted inhibitory cells develop cell-type appropriate molecular characteristics and visually evoked responses. In adult mice impaired by deprivation during the juvenile critical period, transplantation also recovers both visual cortical responses and performance on a behavioral test of visual acuity. Plasticity and recovery are induced when the critical period would have occurred in the donor animal. These results reveal that the focal reactivation of visual cortical plasticity using inhibitory cell transplantation creates a new critical period that restores visual perception after childhood deprivation.

Embryonic interneurons from the medial, but not the caudal ganglionic eminence trigger ocular dominance plasticity in adult mice

“…Most recently, however, it has been shown that somatostatin-containing, dendrite-innervating interneurons, which also arise from the MGE, are equally capable of inducing ocular dominance plasticity (Tang et al 2014). It is, therefore, remarkable that CGE explants, which give rise to diverse forms of mature interneurons, failed to induce plasticity in the present as well as in a concurrent (Davis et al 2015) study. In both studies, the transplanted CGE-derived cells preferentially settled in deep cortical layers, although intrinsic inhibitory interneurons from the CGE are mostly found in superficial layers (Miyoshi et al 2010).…”

“…While it has been shown that they increase both inhibition of intrinsic excitatory cells (Alvarez-Dolado et al 2006;Southwell et al 2012) and ocular dominance plasticity (Davis et al 2015) independently of their density, a direct augmentation of inhibition by diazepam treatment does not induce plasticity in adult mice (Fagiolini and Hensch 2000). Moreover, the opposite intervention, namely reducing inhibition, can also reinstate ocular dominance plasticity in adult animals (Harauzov et al 2010).…”

“…Davis and colleagues have recently shown that plasticity induced by a transplantation of MGE cells into the adult mouse visual cortex could be used to rescue amblyopia (Davis et al 2015). If confirmed, that would signify that additional inhibitory interneurons bypass all plasticitylimiting mechanisms, which could therefore be assumed to act through the intrinsic interneurons.…”

Seeing Anew through Interneuron Transplantation

“…In this issue of Neuron, Davis et al (2015) show that transplantation of embryonic inhibitory interneurons can reactivate critical period plasticity and reverse amblyopia in the visual cortex of adult mice.…”

“…As exciting as these results were, however, a major limitation of this study was that transplantation was done in very young, pre-criticalperiod recipients ( Figures 1A and 1B), severely limiting its potential in clinical applications. In a study published in this issue of Neuron, Davis and colleagues in the Gandhi lab overcame this limitation by performing the vital, yet daunting, experiment of transplanting embryonic inhibitory neurons into adult mice (Davis et al, 2015).…”