Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item Auditory cortical response to spectrotemporally dynamic stimuli during passive listening and behavior(2022) Liu, Ji; Butts, Daniel; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Our sensory system is bombarded with information that can change whimsically and yet we make sense of the flow of the information effortlessly. How does the brain encode such richly dynamic stimuli? Specifically, how does the auditory system encode rich spectral and temporal aspects of the stimulus and how does it depend on the behavioral state of the animal? My study aims to answer these questions within the scope of mouse auditory cortex (ACX) using imaging techniques on various scales. Firstly, I studied how the ACX encodes one temporal aspect of the sound, specifically the onset and the offset. I found that offset responses dominated ACX at high sound levels and their strength depended on auditory cortical fields. Moreover, ACX neurons likely inherit their offset responses from thalamocortical input, which is further processed by local cortical microcircuit. Second, I studied the spectral tuning properties of layer 2/3 neurons in mouse ACX using two-tone stimuli. This study revealed the complex inhibitory sideband structures not only in excitatory and inhibitory neurons, but also in feedforward input from auditory thalamus. These complex structures showed a higher degree of feature selectivity of auditory neurons beyond what is predicted by conventional tuning, and thus auditory cortical responses are highly dependent on the spectral context. These two studies focused on passive listening, but cortical responses could depend on the behavioral state of the animal. The predictive coding theory proposes that sensory cortical responses are a form of error response signaling when sensory input failed to conform with predictions from higher order brain areas. Thus, to study the encoding of spectrotemporally dynamic stimulus under active engagement and to test the predictive coding theory, I designed a novel behavior paradigm that allowed the animal to interact with the sound stimulus and studied the cortical responses to not only the combination of sensory information and the animal’s action but also the introduced perturbation. Together, this dissertation combined advanced imaging techniques and innovations in experimental designs to provide new insight into how ACX encodes sound stimulus under various scenarios.Item Subplate neurons and their role in the functional maturation of the brain(2016) Sheikh, Aminah; Kanold, Patrick O; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Normal brain development is crucial for the proper maturation of neural circuits and cognitive functioning. White matter brain injury during development results in disruption of normal brain maturation and consequently increases risk of developing disorders such as epilepsy and cerebral palsy. Crucial for the proper development of thalamocortical circuits are a transient population of neurons in the developing subcortical white matter of the brain referred to as subplate neurons (SPNs). SPNs are among the first cortical neurons to be born and are necessary for normal functional development of the cerebral cortex. This dissertation begins by studying the effect of SPN removal in the neonatal rat somatosensory cortex (S1). After subplate ablation in the S1 barrel region, we find that removal of SPNs prevents the development of the barrel field in L4, and in vitro recordings reveal that thalamocortical inputs to layer 4 neurons are weak. This dissertation then progresses to investigating the effects of a more clinically relevant and common brain injury among humans, neonatal hypoxia-ischemia (HI), which causes brain damage specific to different brain structures over development. In the preterm human, HI results in damage to subcortical developing white matter, referred to as periventricular leukomalacia (PVL). From other studies we know that HI can damage SPNs however, it is unclear how HI and its differing severities alters SPN circuits. This dissertation uses a rat model of HI in which either mild or moderate HI was induced at postnatal day (P)1. To investigate the functional synaptic connectivity changes of SPNs and layer 4 neurons in both injury categories, this dissertation also uses laser-scanning photostimulation (LSPS) combined with whole-cell patch clamp recordings in acute thalamocortical slices of rat A1 over development. Our results suggest that SPNs are uniquely susceptible to HI and that HI causes a rearrangement of SPN circuits. This leads to abnormal cortical function observed after HI. Results from these studies help fill in crucial gaps in the understanding of not only how important SPNs are in the proper development of multiple sensory regions, but also how vulnerable they are to hypoxic-ischemic brain injury.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.Item Anatomical and Physiological Characterization of the Turtle Brain Stem Auditory Circuit(2014) Willis, Katie Leann; Carr, Catherine E; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The goal of this dissertation is to add to understanding of the evolution of hearing by studying the testudine taxon. This dissertation focuses on central auditory processing in the context of evolution. The experiments described are designed to give insight into how binaural hearing evolved. Follow the findings of Christensen-Dalsgaard and colleagues (2012) that an amphibious turtle had lower hearing thresholds under water than in air and that this difference is conferred by resonance of the middle ear cavity, I examined middle ear cavities across families of Testudines. I found that middle ear cavity structure and function is shared by all testudines (Willis, et al., 2013). Modern neuroanatomical tract tracing techniques were used to understand the connections among the auditory nuclei in the brain stem of the turtle. Turtles have brain stem nuclei that are connected in the same pattern as the other reptiles, including birds. These nuclei are nucleus angularis, nucleus magnocellularis, nucleus laminaris, superior olive, and torus semicircularis. Details of neuron structure were also examined and quantified. Finally, I developed an isolated head preparation that enables in vivo-like physiological recording. As proof of principle, neurons were characterized by best frequency response, threshold, phase locking. Additionally, binaurally responsive neurons were found, which have a range of interaural time difference sensitivity responses. Although the evolutionary position of testudines is not yet resolved, it is most likely that testudines share their most recent common ancestor with the archosaurs. I hypothesize that testudines likely reflect the ancestral condition of auditory processing for the archosaur clade. All experiments described in this dissertation were performed according to the guidelines approved by the Marine Biological Laboratory (Woods Hole, MA, USA), the University of Maryland Institutional Animal Care and Use Committees (IACUC) and the Danish National Animal Experimentation Board (Dyreforsøgstilsynet).