Pallas, S. L. | bioRxiv Science

bioRxiv2018

Dynamic alterations of retinal EphA5 expression in retinocollicular map plasticity

The topographically ordered retinocollicular projection is an excellent system for studying the mechanism of axon guidance. Gradients of EphA receptors in the retina and ephrin-As in the superior colliculus (SC) pattern the anteroposterior axis of the retinocollicular map, but whether they are involved in map plasticity after injury is unknown. Partial damage to the caudal SC at birth creates a compressed, complete retinotopic map in the remaining SC without affecting visual response properties. Previously, we found that the gradient of ephrinA expression in compressed maps is steeper than normal, suggesting an instructive role in compression (Tadesse et al., 2013). Here we measured EphA5 mRNA and protein levels after caudal SC damage in order to test the hypothesis that changes in retinal EphA5 expression occur that are complementary to the changes in collicular ephrin-A expression. We find that the nasotemporal gradient of EphA5 receptor expression steepens in the retina and overall expression levels change dynamically, especially in temporal retina, supporting the hypothesis. This change in receptor expression occurs after the change in ephrin-A ligand expression. We propose that changes in the retinal EphA5 gradient guide recovery of the retinocollicular projection from early injury. This could occur directly through the change in EphA5 expression instructing retino-SC map compression, or through ephrinA ligand signaling instructing a change in EphA5 receptor expression that in turn signals the retinocollicular map to compress. Understanding what molecular signals direct compensation for injury is essential to developing rehabilitative strategies and maximizing the potential for recovery.

neuroscience↗

bioRxiv2018

TrkB activation during a critical period mimics the protective effects of early visual experience on the stability of receptive fields in adult superior colliculus

During a critical period in postnatal development, spontaneous and evoked retinal activity shape nascent visual pathways in an adaptive fashion. Visual experience increases transcription of the neurotrophin BDNF, activating the BDNF receptor TrkB, which promotes maturation of parvalbumin (PV) positive inhibitory interneurons, a process thought to open a critical period for ocular dominance plasticity in visual cortex. Development of perineuronal nets around PV neurons limits plasticity, ending the critical period and restricting adult plasticity. Another form of critical period plasticity is receptive field (RF) refinement. Spontaneous activity alone is sufficient for spatial refinement of visual receptive fields in superior colliculus (SC) and visual cortex (V1), but visual experience during an early critical period is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al. 2005, 2011; Carrasco & Pallas 2006; Balmer & Pallas 2015a). We report here that deprivation-induced RF enlargement in adulthood has a behavioral consequence; it impairs fear responses to looming objects in mice and hamsters. The mechanism through which early experience protects RFs from deprivation-induced loss of inhibition in adulthood is unknown. Given that the loss of RF refinement in SC does not occur until adulthood, and that inhibitory PV neurons and perineuronal nets are rare in SC, we asked whether or not BDNF-TrkB signaling was involved. We find that early TrkB activation is necessary and sufficient to maintain visual RF refinement in adulthood, suggesting a common signaling pathway for maturation of inhibition across neuronal subtypes and locations within the visual pathway.\n\nSignificance StatementReceptive field refinement in superior colliculus (SC) differs from more commonly studied examples of critical period plasticity in visual pathways in that it does not require visual experience to occur; rather spontaneous activity is sufficient. Maintenance of refinement requires brief, early exposure to light to stabilize inhibition beyond puberty. This type of inhibitory plasticity must not depend on parvalbumin (PV)-containing GABAergic interneurons or on the formation of perineuronal nets, because these are very uncommon in SC. Nonetheless, we find that TrkB activation during a critical period can substitute for visual experience in maintaining receptive field refinement into adulthood, and that this maintenance is beneficial to visual survival behaviors. Thus, multiple types of plasticity converge on the same neurotrophin-dependent signaling cascade.

neuroscience↗