TrkB Activation During a Critical Period Mimics the Protective Effects of Early Visual Experience on Perception and the Stability of Receptive Fields in Adult Superior Colliculus

Abstract

During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al. 2005(Carrasco et al. , 2011Carrasco & Pallas 2006;Balmer & Pallas 2015a). In visual cortex (V1), brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Hanover et al., 1999;Huang et al., 1999;Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33-40) in DR subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in DR animals.We also report here that deprivation-or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli, and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between V1 and SC. Significance 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 beyond puberty requires a brief, early exposure to light in order to stabilize the lateral inhibition that shapes receptive fields. We find that 3 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, as in some other types of plasticity, TrkB signaling plays a crucial role in RF refinement.

Multiple Postsynaptic Protein Levels in Adult Superior Colliculus Are Unaffected by Dark Rearing from Birth

“…We have reported here that at the resolution level of Western blots, visual deprivation-induced failure to maintain refined RFs in SC does not appear to involve changes in GABA AR or NMDAR subunit composition, inhibitory or excitatory scaffolding protein expression, or chloride pump ratios. These results exclude several possible mechanisms that could explain the reduced GABAAR signaling reported in DR adult SC (Carrasco et al, 2011), and emphasize that activity-dependent regulation of GABA expression is the primary mechanism underlying TrkB mediated RF refinement maintenance (Mudd et al, 2019). The finding that a change in GABA levels could affect neural plasticity in adulthood has important implications for treatment of memory impairments or brain injury in adults.…”

“…In apparent contradiction to this common view, spontaneous activity is sufficient for refinement of receptive fields in both visual cortex (V1) and superior colliculus (SC) in dark reared (DR) Syrian hamsters, and early light exposure is necessary only for maintenance of refinement in adulthood (Balmer and Pallas, 2015a;Carrasco and Pallas, 2006;Carrasco et al, 2005;Mudd et al, 2019). Pharmacological activation of TrkB receptors can mimic the effects of early light exposure in DR hamsters, resulting in long-term maintenance of refined receptive fields and visual acuity (Mudd et al, 2019). Without early visual experience, lateral inhibition in SC declines and RFs expand in hamsters, leading to a decrease in visual acuity beginning at about two months of age (Balmer and Pallas, 2015a;Carrasco et al, 2005;Mudd et al, 2019).…”

“…In some mammals, visual deprivation is reported to delay or prevent refinement, prolonging critical period plasticity (Cynader and Mitchell, 1980;Fagiolini et al, 1994;Lee and Nedivi, 2002;Mower, 1991;Mower et al, 1985;Nakadate et al, 2012). In apparent contradiction to this common view, spontaneous activity is sufficient for refinement of receptive fields in both visual cortex (V1) and superior colliculus (SC) in dark reared (DR) Syrian hamsters, and early light exposure is necessary only for maintenance of refinement in adulthood (Balmer and Pallas, 2015a;Carrasco and Pallas, 2006;Carrasco et al, 2005;Mudd et al, 2019). Pharmacological activation of TrkB receptors can mimic the effects of early light exposure in DR hamsters, resulting in long-term maintenance of refined receptive fields and visual acuity (Mudd et al, 2019).…”

“…Pharmacological activation of TrkB receptors can mimic the effects of early light exposure in DR hamsters, resulting in long-term maintenance of refined receptive fields and visual acuity (Mudd et al ., 2019). Without early visual experience, lateral inhibition in SC declines and RFs expand in hamsters, leading to a decrease in visual acuity beginning at about two months of age (Balmer and Pallas, 2015a; Carrasco et al ., 2005; Mudd et al ., 2019).…”

Purinergic Modulation of Activity in the Developing Auditory Pathway

“…Since the seminal work of Hubel and Wiesel in the visual system [194][195][196] it is well established that specific neuronal activity during critical developmental periods is required to produce high precision and strength of synaptic contacts in adult neuronal networks [197,198]. Spontaneous neuronal activity can be observed in many systems before the onset of sensory processing, thereafter becoming stimulus-evoked, and thus representing early sensory experience.…”