Biology

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    Mechanisms contributing to opsin expression divergence in the visual system of African Cichlids
    (2018) Nandamuri, Sri Pratima; Carleton, Karen L; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Vision is an important sensory modality, guiding fundamental tasks such as foraging, escaping from predators, identification of conspecifics and selection of mates. As such, animals exhibit a wide variety of adaptations to spectrally tune their visual systems to closely match the environment. This extensive variation in visual system tuning is achieved both via genetic changes as well as environmental induced plasticity. Lacustrine cichlids of East Africa are famous for their expedited adaptive radiations. Cichlids in these rift lakes inhabit a diverse range of light environments, from the murky red-shifted waters of Lake Victoria to clear Lake Malawi. Consequently, African cichlids have some of the most diverse visual systems among vertebrates on the planet, with species expressing different combinations of seven cone opsin genes. This differential expression is under genetic control and leads to drastic differences in the visual sensitivities between closely related species. Moreover, cichlid species often exhibit plastic changes in opsin expression due to alterations in environmental light conditions. The diversity of genetically determined visual palettes and the variation in expression due to plastic changes offers an excellent opportunity to study the proximate mechanisms governing opsin expression divergence in this group. Utilizing a hybrid cross between two species varying in opsin expression, we show that divergent expression of cone opsins is regulated by multiple quantitative trait loci (QTLs). Most of these QTLs are located in trans to the opsins, with the exception of one QTL in cis to the SWS1 opsin. Further fine-mapping of the cis-QTL revealed a deletion in the promoter of the SWS1 gene that is associated with a decrease in its expression. Additionally, performing two reciprocal experiments, we show that adult cichlids from Lake Malawi show rapid and reversible plastic changes in opsin expression due to differences in lighting conditions. These studies show that both predetermined genetic factors and environmental inputs contribute to opsin expression divergence in cichlids. These factors enable short term and ultimately long-term adaptation to changing habitats, facilitating the survival and perhaps speciation of these fantastic fishes.
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    Development and plasticity of the functional laminar mesoscale organization of the primary auditory cortex
    (2016) Solarana, Krystyna; Kanold, Patrick O; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Early sensory experience is fundamental for proper structural and functional organization of the brain. A brain region that particularly relies on sensory input during a critical period of development is the primary auditory cortex (A1). The functional architecture of A1 in adult mammals has been widely studied on a macroscale and single-cell level, and it is evident that this sensory area is characterized by a tonotopic gradient of frequency preference and that individual auditory neurons are tuned to complex features of acoustic stimuli. However, the development of microcircuits within A1 and how experience shapes this mesoscale organization during different plasticity windows is not known. The work in this dissertation uses in vivo two-photon calcium imaging in mice to investigate how the population dynamics of auditory neurons within thalamorecipient layer 4 and supragranular layers 2/3 change over development – from before ear opening, through the critical period for auditory spectral tuning, and on to mature adult circuitry. Furthermore, this dissertation explores how brief visual deprivation has the power to initiate compensatory, cross-modal plasticity mechanisms and restructure network circuitry in the adult auditory cortex, after the critical period for developmental plasticity has closed. Results from these studies fill crucial gaps in our understanding of experience-dependent cortical circuit development and refinement by showing that the spatial representation of sound frequency is shaped by sensory experience, teasing apart the underlying laminar-specific differences in microcircuitry changes, and indicating an overall dissociation of plasticity of single-cell, mesoscale, and macroscale network properties.
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    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.