UMD Theses and Dissertations

Permanent URI for this collectionhttp://hdl.handle.net/1903/3

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.

More information is available at Theses and Dissertations at University of Maryland Libraries.

Browse

Filters

2014 - 201922020 - 20231

Settings

Subject: search.filters.subject.critical period

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    the regulation of critical period for ocular dominance plasticity
    (2014) Gu, Yu; Quinlan, Elizabeth M; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The experience dependent plasticity of stimulus selectivity, including ocular dominance plasticity, is highest during a postnatal critical period. The developmental constraint on this plasticity is thought to underlie the inability to recover from amblyopia in adults, which has generated interest in understanding the mechanisms for the initiation and termination of the critical period. Previously, it had been shown dark exposure initiated in adulthood (P90) reactivates robust ocular dominance plasticity in the visual cortex. In this thesis, I showed dark exposure initiated earlier (P45-55) in postnatal development does not facilitate rapid ocular dominance plasticity, demonstrating the presence of a refractory period for the regulation of synaptic plasticity by visual deprivation. Using an anesthetic other than barbiturate revealed that ocular dominance plasticity persists much later in postnatal development (up to ~ P55), which can be inhibited by diazepam, a positive allosteric modulator of ligand bound GABAARs, suggesting a regulatory mechanism that is upstream of inhibitory synaptic transmission. To test this, I used NARP and NRG1-ErbB4 to manipulate excitation onto FS (PV) INs, a major subtype of inhibitory neurons which exert powerful perisomatic inhibition onto principal neurons in the visual cortex. NARP is an activity dependent pentraxin which has been shown to accumulate AMPARs onto FS (PV) INs. Transgenic deletion of NARP decreases the number of excitatory synaptic inputs onto FS (PV) INs and reduces net excitatory synaptic drive onto FS (PV) INs. Accordingly, the visual cortex of NARP -/- mice is hyperexcitable and unable to express ocular dominance plasticity, although many aspects of visual function are normal. NRG1 is an activity dependent neutrophic factor which is proposed to promote excitability and excitatory synaptogenesis onto FS (PV) INs. Pharmacological manipulation of the NRG1-ErbB4 pathway can regulates the excitability of FS and RS neurons in visual cortex, and promotes or inhibits the expression of ocular dominance plasticity, depending on the state of maturation of cortical circuitry. Importantly, manipulations of the excitability of FS and RS neurons into the permissive range can enable the expression of ocular dominance plasticity, at any age, which holds promise to future treatment of clinical disorders such as amblyopia.