Theses and Dissertations from UMD
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Item Reactivation of plasticity in the adult visual cortex by control of neuronal excitability(2023) Borrell, Andrew; Quinlan, elizabeth; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Amblyopia is a highly prevalent form of monocular vision loss that impacts between 1-4% of the worldwide population. Amblyopia is characterized by decreased visual acuity in a single eye and is highly refractory to treatment past a “critical period” of heightened plasticity during early adolescence (>5 years of age). The time course of this critical period is due to the developmental regulation of experience-dependent synaptic plasticity in the primary visual cortex (V1). During early development, visual experience drives activity-dependent changes in NMDA-R subunit composition, refines the convergence of binocular inputs, and promotes the maturation of inhibitory circuits in V1. The transient conditions in V1 that permit the refinement of cortical circuits during the critical period also render V1 vulnerable to the detrimental impacts of amblyopia.The expression of critical period plasticity requires visual experience: dark-rearing delays the onset and closure of the critical period and prevents the experience- dependent change in NMDA-R subunit composition. It is now understood that visual experience in adulthood is also important for the expression of plasticity: sensory deprivation via prolonged dark exposure (DE) rejuvenates the V1 circuit to a juvenile-like state via a homeostatic increase in spontaneous excitatory in V1. Subsequent visual experience during light reintroduction (LRx) enables the expression of critical period plasticity and the functional rewiring of thalamocortical inputs to V1. Here I asked how the homeostatic increase in spontaneous activity induced during DE is regulated by visual experience immediately following LRx (LRxi), and during one day of subsequent day of LRx (LRxs). I demonstrate that the homeostatic increases in spontaneous excitatory neuron activity is maintained during LRxi and is accompanied by increased evoked excitatory neuron activity. These increases in averaged spontaneous and evoked activity returned to baseline by LRxs. Next, I asked whether decreased spontaneous activity following one day of LRx was necessary for the reactivation of critical period plasticity. Using the mouse model of ocular dominance plasticity (ODP) and cell-type specific expression of inhibitory chemogenetic Gi-DREADD receptors in fast spiking Parvalbumin-expressing interneurons, I demonstrated that prolonged disinhibition of spontaneous V1 activity during LRx occludes the reactivation of ODP, but not the reactivation of the plasticity of acuity. These results demonstrate the differing contribution of cortical mechanisms to ocular dominance versus acuity in the regulation of the critical period plasticity, and the necessity of the decrease in average spontaneous activity for the re-expression ODP.Item REACTIVATION OF PLASTICITY BY DARK EXPOSURE PROMOTES ANATOMICAL AND PHYSIOLOGICAL RECOVERY FROM CHRONIC MONOCULAR DEPRIVATION IN ADULTS(2012) Montey, Karen; Quinlan, Elizabeth M; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chronic monocular deprivation, initiated early in postnatal life and maintained until adulthood, causes severe amblyopia, characterized by a significant decrease in strength and selectivity of visual cortical responses evoked by stimulation of the deprived eye. Amblyopia is highly resistant to reversal in adulthood, but binocular visual deprivation through dark exposure can be used to promote recovery from chronic monocular deprivation. To identify the locus of the changes in excitatory synaptic transmission that accompany the response to, and recovery from chronic monocular deprivation, I quantified the density of dendritic spines throughout the depth of the primary visual cortex. I demonstrate that chronic monocular deprivation induces a significant loss of dendritic spine density in all cortical laminae. Importantly, recovery of visual responses induced by dark exposure followed by reverse deprivation is accompanied by a significant recovery of dendritic spine density. As the majority of excitatory synaptic transmission is mediated by spine synapses, this suggests significant loss and recovery of excitatory synaptic density during loss and recovery of vision. The observation that mid cortical laminae, which are enriched for thalamocortical synapses, participates in the recovery from chronic monocular deprivation in adulthood was unexpected, given that plasticity at thalamorecipient synapses has been demonstrated to be constrained very early in postnatal life. Isolation of the thalamocortical component of the visually evoked potential via cortical silencing confirmed an experience-dependent strengthening during the recovery from amblyopia. This work further supports the hypothesis that dark exposure in adulthood returns the visual cortex to a "juvenile" state, capable of expressing plasticity at thalamocortical synapses. Severe amblyopia is characterized by a loss of the strength and selectivity of visually evoked activity in primary visual cortex. The reduction in visually evoked responses recovers completely when dark exposure is followed by reverse deprivation (open deprived eye, close nondeprived eye). However, the recovery of spatial acuity, measured by performance in a spatial frequency discrimination task, is incomplete. Therefore, I designed a strategy to promote the strengthening of synapses serving the deprived eye that utilizes tetanic visual stimulation. Dark exposure followed by visual tetanus induced a significant strengthening of synapses serving the deprived eye. Importantly, the potentiation of visual responses generalized to novel stimuli without modifying stimulus selectivity. Subsequent repetitive performance of a two-choice spatial frequency discrimination task, promoted a recovery of orientation selectivity and spatial acuity. The combination of dark exposure (to reactivate plasticity), visual tetanus (to promote synaptic strength) and perceptual learning (to promote neuronal stimulus selectivity) may accelerate and enhance recovery of visual functions, thereby optimizing the recovery from severe amblyopia.