Brief dark exposure restored ocular dominance plasticity in aging mice and after a cortical stroke

Abstract

In the primary visual cortex (V1), monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons towards the open eye (Wiesel and Hubel, 1963; Gordon and Stryker, 1996). In V1 of C57Bl/6J mice, this OD-plasticity is maximal in juveniles, declines in adults and is absent beyond postnatal day (PD) 110 (Lehmann and Löwel, 2008) if mice are raised in standard cages. Since it was recently shown that brief dark exposure (DE) restored OD-plasticity in young adult rats (PD70-100) (He et al., 2006), we wondered whether DE would restore OD-plasticity also in adult and old mice and after a cortical stroke. To this end, we raised mice in standard cages until adulthood and transferred them to a darkroom for 10-14 days. Using intrinsic signal optical imaging we demonstrate that short-term DE can restore OD-plasticity after MD in both adult (PD138) and old mice (PD535), and that OD-shifts were mediated by an increase of open eye responses in V1. Interestingly, restored OD-plasticity after DE was accompanied by a reduction of both parvalbumin expressing cells and perineuronal nets and was prevented by increasing intracortical inhibition with diazepam. DE also maintained OD-plasticity in adult mice (PD150) after a stroke in the primary somatosensory cortex. In contrast, short-term DE did not affect basic visual parameters as measured by optomotry. In conclusion, short-term DE was able to restore OD-plasticity in both adult and aging mice and even preserved plasticity after a cortical stroke, most likely mediated by reducing intracortical inhibition.

Amblyopia: New molecular/pharmacological and environmental approaches

“…For example, rats rendered amblyopic by chronic monocular deprivation initiated at eye opening recovered visual acuity when 10 days of dark exposure in young adulthood (P70–100) were followed by binocular vision or reverse occlusion (He et al, 2007). Remarkably, short-term dark exposure (10 days) can reinstate visual cortical plasticity even in very old mice (P535; Stodieck et al, 2014). However, the effects of dark exposure on adult plasticity may vary across species; while 10 days of darkness enhanced OD plasticity in juvenile kittens, this treatment failed to restore OD plasticity in adult cats (Duffy et al, 2016).…”

“…A reduction in inhibitory synaptic transmission by dark exposure may be a feature in common with EE. As with environmental enrichment (Greifzu et al, 2014), dark exposure may work through a rejuvenation of intracortical inhibition, including a reduction of the excitatory drive onto fast-spiking interneurons (Huang et al, 2010; Gu et al, 2016) and a decrease in the number of parvalbumin-expressing inhibitory cells and surrounding peri-neuronal nets (Stodieck et al, 2014). Indeed, the adult recovery from long-term monocular deprivation can be stimulated by a reduction in the activity of inhibitory neurons (Kaneko & Stryker, 2014).…”

“…Transplantation of embryonic inhibitory neurons into the postnatal visual cortex induces a second critical period of OD plasticity after the normal one (Southwell et al, 2010; Tang et al, 2014; Isstas et al, 2017). Plasticity is also enhanced in the adult visual cortex by decreasing perineuronal nets that predominantly enwrap the PV cells by pharmacological (Pizzorusso et al, 2002) or behavioral interventions, such as environmental enrichment (Sale et al, 2007) or dark exposure (Stodieck et al, 2014). A reduction in the excitatory drive to PV cells (Huang et al, 2010; Gu et al, 2016) and an increase in spine density and NMDA-Rs (Yashiro et al, 2005; He et al, 2006; Philpot et al, 2007; Montey & Quinlan, 2011) may also contribute to the enhanced plasticity that occurs with dark exposure.…”

Optimization of visual training for full recovery from severe amblyopia in adults

“…In addition, dark exposure scales up excitatory synapses on principle neurons, increases visual cortex excitability, and expands the integration window for spike-timing dependent plasticity (Goel and Lee 2007;He et al 2007;Guo et al 2012). The success of dark rearing, and other manipulations, such as environmental enrichment, to promote the recovery from amblyopia in rodents and felines (He et al 2006;Sale et al 2007;Maya Vetencourt et al, 2008;Duffy and Mitchell 2013;Stodieck et al, 2014) likely depends on the reactivation of these and other forms of activity-dependent plasticity (Kuo and Dringenberg 2009;Harauzov et al 2010;Mainardi et al 2010;Djurisic et al 2013) that are engaged by visual perceptual learning (Baroncelli et al 2012;Montey et al 2013).…”

Seeing Anew through Interneuron Transplantation

“…Interestingly, changing the animal's rearing conditions is able to induce new plasticity in adult visual cortex and promote recovery from amblyopia, and this includes two seemingly opposite manipulations: environmental enrichment and dark exposure. Both manipulations were shown to reduce intracortical inhibition and PNN density He et al, 2006He et al, , 2007Sale et al, 2007;Stodieck et al, 2014), suggesting that they may work through similar mechanisms to reopen critical period plasticity.…”