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

Abstract

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.