Monocular enucleation alters retinal waves in the surviving eye

Abstract

BackgroundActivity in neurons drives afferent competition that is critical for the refinement of nascent neural circuits. In ferrets, when an eye is lost in early development, surviving retinogeniculate afferents from the spared eye spread across the thalamus in a manner that is dependent on spontaneous retinal activity. However, how this spontaneous activity, also known as retinal waves, might dynamically regulate afferent terminal targeting remains unknown.MethodsWe recorded retinal waves from retinae ex vivo using multi-electrode arrays. Retinae came from ferrets who were binocular or who had one eye surgically removed at birth. Linear mixed effects models were used to investigate the effects of early monocular enucleation on retinal wave activity.ResultsWhen an eye is removed at birth, spontaneous bursts of action potentials by retinal ganglion cells (RGCs) in the surviving eye are shorter in duration. The shortening of RGC burst duration results in decreased pairwise RGC correlations across the retina and is associated with the retinal wave-dependent spread of retinogeniculate afferents previously reported in enucleates.ConclusionOur findings show that removal of the competing eye modulates retinal waves and could underlie the dynamic regulation of competition-based refinement during retinogeniculate development.

A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves

“…The recent visualization of a subset of calcium waves traveling from the retina to the SC in a simultaneous bilateral manner raised the hypothesis that interactions brought about by an R-R projection could be responsible for synchronizing retinal waves [ 6 ]. This idea is further supported by recent results demonstrating that enucleation of one eye alters retinal waves in the remaining eye [ 20 ].…”

Unraveling Myelin Plasticity

“…Eye enucleation in a non-degenerative mouse model reduces axonal diameter and myelination, supporting the notion that axon caliber is a main regulatory factor of myelination. Although there is a correlation between axon diameter and myelination, it is important to note that knocking out Pten alters growth factor signaling (Goebbels et al, 2017), and that enucleation alters spontaneous firing in the control eye (Failor et al, 2018), raising the possibility that diameter alone is not the only mechanism regulating myelination (Friede, 1972;Lee et al, 2012), or that different axons are myelinated by different mechanisms (Koudelka et al, 2016). Additionally, diameter alone does not explain how the same axon can be differentially myelinated along its length, nor how axons of the same diameter can be either myelinated or remain unmyelinated (Tomassy et al, 2014).…”

Ocular Necessities: A Neuroethological Perspective on Vertebrate Visual Development

“…Early in development, in some species, bursts of action potentials spontaneously initiate and travel across the retina in a wave-like fashion. These spontaneous, correlated action potentials, termed “retinal waves,” are known to play an important role in several processes of mammalian visual development, such as regulating the formation of gap junctions between retinal ganglion cells (RGCs) [ 6 ]; modulating inter-retinal coordinated activity [ 7 ]; influencing the receptive fields of neurons in visual cortex, superior colliculus, and lateral geniculate nucleus (reviewed in [ 8 ]); and guiding refinement of retinotopic maps [ 9 , 10 ]. Despite their profound importance for mammalian visual development, and despite the early seminal work on spontaneous retinal activity carried out in turtles – first, with multiunit electrophysiological recordings [ 11 , 12 ], then with the direct observation of waves via calcium imaging [ 13 ] – few researchers have systematically addressed the presence and function of spontaneous retinal waves in the non-mammalian vertebrate lineage.…”

“…Mammalian retinal waves not only guide the formation of connections between the retina and the lateral geniculate nucleus [ 60 , 61 ], but they also regulate the formation of gap junctions between RGCs within the retina [ 6 ]. Intriguingly, retinal waves additionally modulate inter-retinal activity in mammals, with monocular enucleation influencing the dynamics of retinal waves in the remaining eye [ 7 ]. These observations could be explained, at least in part, by a transient retino-retinal projection that may serve to synchronize retinal wave activity between the two eyes [ 10 ].…”