Biology Theses and Dissertations
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Item NEURAL BASIS OF VIBRATION DETECTION IN LEPIDOSAURIAN REPTILES(2024) Han, Dawei; Carr, Catherine E.; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)There are three potential pathways for detection of substrate vibration: cochlear, otolithic and somatosensory, reviewed in chapter one. How different lepidosaurian reptiles detect substrate vibration from these three pathways was explored from neuroanatomical and physiological perspectives. In chapter two, I described vibration sensitivity and the organization of the brainstem cochlear nuclei in the western snake (Pantherophis obsoletus). The western ratsnake is sensitive to low-frequency vibrations, comparable to other snakes. It has two first-order cochlear nuclei, nucleus magnocellularis (NM) and nucleus angularis (NA), similar to other reptiles. NM is small, while NA is relatively robust. In chapter three, I examined the connections and response properties of nucleus vestibularis ovalis (VeO) in the hindbrain of the tokay gecko (Gekko gecko). VeO receives input from the saccule, and connections of VeO mirror those of the cochlear nuclei, including an ascending projection to the central nucleus of the torus semicircularis. VeO neurons are sensitive to low-frequency vibration. In chapter four, I revisited a classic study to determine the connections and response properties of the snake torus semicircularis. In the western ratsnake, the torus can be divided into a central nucleus and a paratorus, the latter receiving input from the spinal cord, nucleus myelencephali dorsalis in the spinomedullary junction, as well as auditory nuclei. Toral neurons are sensitive to low frequency vibration and have heterogenous response characteristics. In chapter five, I discuss future directions based on findings in my dissertation and highlight the importance of vibration detection for lepidosaurs.Item INTERACTIONS OF SOCIAL EXPERIENCE, ALCOHOL SENSITIVITY, AND THE SEROTONERGIC SYSTEM(2024) Ho, Ta-wen; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Social isolation has been shown to correlate with increased alcohol consumption in various animal species. In humans, a decreased sensitivity to acute alcohol is correlated with future alcohol dependence and addiction. A plausible explanation for this correlation is that alcohol sensitivity decreases after isolation; however, our understanding of the mechanistic interaction between social isolation and sensitivity to acute alcohol is still in its infancy. The serotonergic system is one promising candidate that could be involved in this interaction because of its wide range of behavioral and physiological effects, especially those related to social experiences. In my dissertation, I investigated the roles of the serotonergic (5-HT) system with three separate aims: In the first aim, I measured the effects of several 5-HT agents (neurotoxin, reuptake blocker, and receptor agonist/antagonists) in freely-behaving crayfish that were communally housed (COMs) or individually isolated (ISOs) prior to ethanol (EtOH) exposure. I found that 5-HT is important in regulating the social differences in EtOH sensitivity, and 5-HT2βPRO receptors emerged as candidates to produce this interaction between 5-HT and EtOH. My results from this aim suggest that these receptors are downregulated in isolated crayfish, leading to reduced behavioral EtOH sensitivity. The second aim employed single-cell neurophysiology and pharmacology in the lateral giant (LG) circuit of reduced ex vivo crayfish preparations to investigate the cellular-molecular mechanisms that underlie the interaction between 5-HT and specific EtOH receptor targets. I found that the LG neurons are stimulated by EtOH, and social differences in EtOH sensitivity between COMs and ISOs are paralleled at the level of these single neurons. Specifically, my results suggest that social isolation causes downregulation of 5-HT2βPRO receptors and 5-HT1αPRO receptors on the LG neurons and upregulation of these receptors subtypes in GABAergic neurons that send feed-forward inhibition onto the LG neurons. In my third aim, I developed a wearable, miniature, cyclic voltammetry device that is capable of detecting (injected) monoamine neurotransmitters (including 5-HT) in freely-behaving crayfish. With improved sensor sensitivity in the future, this will allow measurements of 5-HT release patterns in crayfish with different social histories, including during EtOH exposure. Together, the results from my dissertation will inform work in other model systems and improve our understanding of the interactions between social experience, the 5-HT system, and alcohol use.Item Sculpting Sounds: INTRINSIC PHYSIOLOGY AND INHIBITORY ANATOMY OF THE AVIAN AUDITORY BRAINSTEM(2024) Baldassano, James; MacLeod, Katrina; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Soundwaves are rapidly modulated, multi-dimensional stimuli. The cochlea decomposes these signals into frequency and intensity information which is conveyed via the auditory nerve into the brain. How does the brain manage to extract these multidimensional signals from auditory nerve activity? How does it sculpt this input so that both the microsecond precision of “where?” and the spectrotemporal modulations of “what?” are encoded with high fidelity? Birds are powerful models for studying early auditory processing because they interact with sounds similarly to mammals but have a simpler neuronal architecture. We describe the intrinsic physiology and anatomy and auditory brainstem neurons involved in spectrotemporal processing. In birds, the auditory nerve synapses onto two anatomically distinct cochlear nuclei, cochlear nucleus magnocellularis (NM) which encodes frequency/timing information, and the more heterogeneous cochlear nucleus angularis (NA) which encodes intensity information. NA has been shown to encode the acoustic envelope, likely through a subset of neurons that respond preferentially to modulations in their inputs via an adaptive spike threshold. We first examined the intrinsic basis of this adaptive threshold and found that a dendrotoxin-sensitive low threshold potassium conductance is responsible for it. In addition to the intrinsic properties of neurons, inhibition sculpts a number of auditory processes. The majority of inhibition in the avian auditory brainstem originates in the superior olivary nucleus (SON), which has multiple response types & projects either to multiple lower order ipsilateral nuclei, including NA & NM, or to the contralateral SON. Retrograde labeling experiments have demonstrated that these projections originate from distinct populations of SON neurons, however it is not clear if there is a relationship between response types and postsynaptic target. We used in vitro electrophysiology and neuronal reconstruction to establish a relationship between response types and targets. While the function of inhibition is well documented in timing circuits, its role in intensity processing is less clear. We used dynamic clamp to model inhibitory conductances while recording from NA neurons in vitro to determine how inhibition impacts the range of inputs that a NA neuron can encode before its firing rate saturates.Item SEROTONIN REGULATES AN OLFACTORY CRITICAL PERIOD IN DROSOPHILA(2024) Mallick, Ahana; Araneda, Ricardo; Gaudry, Quentin; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in sensory systems. Studies in the somatosensory and visual cortices implicate multiple target points of serotonergic modulation, yet the underlying cellular and molecular mechanisms of 5-HT modulation of critical period plasticity remain elusive. Here, we take advantage of the genetically tractable olfactory system of Drosophila to investigate how 5-HT modulates critical period plasticity (CPP) in the CO2 sensing circuit of fruit flies. During the critical period, chronic exposure to CO2 has been shown to increase the volume of the CO2 sensing V glomerulus. We found that 5-HT release by serotonergic neurons in the antennal lobe (AL) is required for increase in the volume of the V glomerulus. Furthermore, signaling via the 5-HT1B, 5-HT2B and 5-HT7 receptors in different neuronal populations is also required during the critical period. Olfactory CPP is known to involve local inhibitory networks and consistent with this we found that knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by olfactory sensory neurons (OSNs). Additionally, 5-HT2B expression in the cognate OSNs sensing CO2 is also essential for CPP indicating that direct modulation of OSNs also contributes to the olfactory CPP. Furthermore, 5-HT1B expression by serotonergic neurons in the olfactory system is also required during the critical period. Our study reveals that 5HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit. Finally, we wanted to isolate the neuromodulatory effects of individual serotonergic neurons. To achieve this, we combined a state-of-the-art technique to sparsely label serotonergic neurons and a computer algorithm to search against 10,000 Gal4 promoter lines and identify candidate lines that would allow individual manipulation of the 110 serotonergic neurons.Item Predictors of Peer Interaction Success for Autistic and Non-Autistic Youth(2024) McNaughton, Kathryn; Redcay, Elizabeth; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Successful peer interactions are a crucial component of mental health and well-being for autistic and non-autistic youth. Factors that influence successful peer interactions are particularly relevant to investigate in middle childhood and adolescence, a developmental period in which peer interactions take on increased importance for mental health. Research into social interactions can involve both individual-level and interindividual-level understanding of interaction outcomes. Individual-level predictors can yield insight into the way one’s own characteristics predict social interaction outcomes, for example, informing theories about how an individual’s social motivation may predict their social enjoyment. However, because research into social interaction challenges and success in autism has historically focused on individual-level contributions of autistic individuals to social interaction outcomes, it is also important to understand interindividual-level mechanisms, such as the similarity or synchrony between individuals, to understand the role both non-autistic and autistic individuals play in shaping social interactions and their outcomes. Therefore, the overarching goal of this dissertation is to evaluate potential neural and behavioral predictors of peer interaction success in autistic and non-autistic youth during middle childhood and adolescence at the individual and interindividual level. First, I demonstrate that neural sensitivity to social-interactive reward is an individual-level predictor of peer interaction enjoyment. Next, I move beyond individual-level neural predictors to interindividual-level neural predictors, providing evidence for how neural similarity to peers may differentially relate to day-to-day interaction success across different interaction types, such as interactions with peers. Finally, I establish smiling synchronization as an interindividual predictor of peer interaction enjoyment. These studies span the neural and behavioral levels of analysis, providing insight into how these levels of analysis can be investigated from both an individual and interindividual perspective. The findings advance understanding of factors that predict peer interaction success, leading to better understanding of opportunities to support successful peer interactions through individual and interindividual interventions with autistic and non-autistic youth.Item HOW BILINGUALS' COMPREHENSION OF CODE-SWITCHES INFLUENCES ATTENTION AND MEMORY(2024) Salig, Lauren; Novick, Jared; Slevc, L. Robert; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Bilinguals sometimes code-switch between their shared languages. While psycholinguistics research has focused on the challenges of comprehending code-switches compared to single-language utterances, bilinguals seem unhindered by code-switching in communication, suggesting benefits that offset the costs. I hypothesize that bilinguals orient their attention to speech content after hearing a code-switch because they draw a pragmatic inference about its meaning. This hypothesis is based on the pragmatic meaningfulness of code-switches, which speakers may use to emphasize information, signal their identity, or ease production difficulties, inter alia. By considering how code-switches may benefit listeners, this research attempts to better align our psycholinguistic understanding of code-switch processing with actual bilingual language use, while also inspiring future work to investigate how diverse language contexts may facilitate learning in educational settings. In this dissertation, I share the results of three pre-registered experiments with Spanish-English bilinguals that evaluate how hearing a code-switch affects attention and memory. Experiment 1a shows that code-switches increase bilinguals’ self-reported attention to speech content and improve memory for that information, compared to single-language equivalents. Experiment 1b demonstrates that this effect requires bilingual experience, as English-speaking monolinguals did not demonstrate increased attention upon hearing a code-switch. Experiment 2 attempts to replicate these results and establish the time course of the attentional effect using an EEG measure previously associated with attentional engagement (alpha power). However, I conclude that alpha power was not a valid measure of attention to speech content in this experiment. In Experiment 3, bilinguals again showed better memory for information heard in a code-switched context, with a larger benefit for those with more code-switching experience and when listeners believed the code-switches were natural (as opposed to inserted randomly, removing the element of speaker choice). This suggests that the memory benefit comes from drawing a pragmatic inference, which likely requires prior code-switching experience and a belief in code-switches’ communicative purpose. These experiments establish that bilingual listeners derive attentional and memory benefits from ecologically valid code-switches—challenging a simplistic interpretation of the traditional finding of “costs.” Further, these findings motivate future applied work assessing if/how code-switches might benefit learning in educational contexts.Item MODULATION OF SIGNALING IN THE ANTERIOR CINGULATE CORTEX AND ITS IMPACT ON DECISION-MAKING(2024) Vazquez, Daniela; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Attentional deficits are defining hallmarks of some of the most prevalent and disruptive neuropsychiatric disorders—including attention deficit hyperactivity disorder (ADHD) and substance abuse disorders. The anterior cingulate cortex (ACC) is a brain region that is highly implicated in shifting attention allocation towards relevant stimuli after unexpected events or outcomes occur. Importantly, increases in attention facilitate flexible learning, as attention allows you to dynamically filter relevant and necessary information during decision-making. My dissertation work seeks to identify the ACC as a novel point of intervention for the treatment of neuropsychiatric and addiction disorders by providing an in-depth perspective on its involvement in cognitive control and attentional processes.My research explores the neural correlates of decision-making by using electrophysiology to record single unit activity while rats perform a complex reward-based decision-making task, and employing chemical, optogenetic, and epigenetic manipulations to modulate attentional correlates in the ACC. I explored the ACC’s role in attention—and how it is impacted by drug use—using electrophysiology to record from ACC neurons as both cocaine-exposed and drug-naïve rats performed a reward-guided decision-making task. Using this task, we found a dose-dependent attenuation of ACC signaling after cocaine self-administration, which was correlated with decreases in task performance and attention to the task. Rats that had self-administered large amounts of cocaine had diminished neural responsiveness to cues, which translated into reductions in behavioral measures of attention, disruptions in cognitive flexibility, and decision-making impairments. These results both supported previous findings establishing the ACC’s role in attentional allocation, and revealed an intake-dependent effect of drugs on decision-making and neural encoding. In aim 2, we wanted to be able to precisely modulate ACC activity in order to better interrogate the role of the ACC in the absence of confounding variables (e.g. cocaine use results in the dysregulation of various neural circuits), and conduct within-subject analyses. Thus, in our next experiment we used optogenetics to inactivate the ACC, and found that ACC inhibition severely impaired task engagement, as evinced by reductions in trial initiations, and trial and session completions—resulting in overall impaired session performance. In order to disambiguate whether these behavioral deficits resulted from ACC impairment dysregulating downstream action-outcome encoding, we performed chemical lesions of the ACC, and recorded neural activity from the dorsomedial striatum (DMS)—a downstream brain region that is importantly involved in goal-directed behavior—as rats performed the previously mentioned decision-making task. Again, we found that ACC lesions resulted in disrupted attention to the task, and similar behavioral deficits to the ones we observed following cocaine use. Interestingly, we found that DMS encoding was minimally impacted, reinforcing that the observed decision-making deficits stem from disruptions in attentional signaling and not dysregulations in downstream action-outcome encoding. In the aforementioned experiments, we employed an array of techniques to dissect how disrupting ACC signaling in a variety of manners impacted task performance and engagement, so for our final experiment we sought to explore a therapeutically relevant way to potentially repair signaling disruptions that lead to the breakdown in attentional signaling. Thus, we turned to epigenetics—specifically, decreasing the expression of HDAC5, an enzyme that is involved in negatively regulating gene expression—to explore whether epigenetic changes might map onto specific alterations of neural activity and behavior. Surprisingly, we found that HDAC5 knockdown in the ACC dysregulates attentional signals that are necessary for flexible and adaptive decision-making. Together, these studies established that signaling in the functional ACC is importantly involved in attention, and that dampening these signals leads to decision-making impairments and decreased task engagement, notably characterized by significant reductions in the proportion of initiated and completed trials, and prolonged periods of inattention.Item EXPLORING NEURAL REPRESENTATIONS IN MACAQUE PRIMARY VISUAL CORTEX THROUGH DATA-DRIVEN MODELS(2024) Bartsch, Felix; Butts, Daniel A; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The study of the primary visual cortex (V1) holds profound significance for our understanding of the neural underpinnings of visual perception. Computational models have emerged as invaluable tools to decode the intricate computations occurring within V1 neurons. This dissertation embarks on a comprehensive exploration of V1 by fitting statistical models to electrophysiological data and scrutinizing model properties. My approach not only provides direct insights into how V1 neurons represent information but also furnishes mathematical descriptions of V1 computations, thereby contributing to the construction of a unified model of V1 function.I begin in Chapter 2 by employing state-of-the-art statistical and machine learning techniques to unravel the high-resolution components of V1 receptive fields as they respond to random bar stimuli. I demonstrate how these models not only replicate classical findings but also offer superior explanations of the computations V1 undertakes. These results highlight how the simultaneous processing of multiple overlapping inputs enables cells to represent high-resolution information while also responding to full-field inputs, an intricate organization unattainable using conventional stimuli. In chapter 3, I expand this modeling approach by adding mechanisms for binocular integration and apply them to data obtained from random bar stimuli that also vary in binocular disparity. This approach reveals that V1 disparity selectivity is enhanced and well characterized using spatial convolutions. Finally, I further modify the approach in chapter 4 to map spatiotemporal receptive fields in luminance and color using data recorded from the fovea and present the first spatiochromatic measurements illustrating the scale of V1 processing at the fovea. I find that color signals operate at lower spatial scales compared to luminance signals, and that receptive field substructure can allow even cells with large receptive fields to represent fine-scale information throughout the fovea.Item Mental Workload Assessment During Upper Limb Prosthetic Training and Task Performance(2023) Gaskins, Peter Christopher; Gentili, Rodolphe J; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Mental workload, defined as the recruitment and allocation of cortical resources in response to task demands, is an integral underlying mechanism of cognitive-motor learning and performance. Although widely examined in individuals without motor impairment, the study of mental workload in a clinical context of motor rehabilitation is limited. In particular, it is not well understood how the cortical processes underlying mental workload adapt over time as individuals learn to operate upper-limb prosthetic devices. In this work, mental workload assessment using electroencephalography (EEG) along with other ancillary measurement tools were employed to examine the recruitment of cognitive-motor processes as individuals learned to operate either a body-powered (BP) or myoelectric (MYO) bypass prosthesis during a ten session upper limb prosthetic training program. The first two studies examined changes in mental workload and cognitive-motor performance as prosthesis users executed tasks requiring transport of objects with the same or different shape/size during a prosthetic training program. Then, these newly trained prosthesis users engaged in activities which manipulated contextual demands to examine how real-world scenarios affect mental workload and cognitive-motor performance. Finally, a preliminary validation of a novel mental workload self-report measure aimed to address the paucity of mental workload measurement tools in upper-limb rehabilitation was implemented. Although these four studies offer a rich and complex pattern of results, the main findings suggested that i) while both prosthetic groups experienced similar levels of cognitive-motor performance by the end of training, the BP group exhibited more refined cortical dynamics and better cognitive-motor efficiency when compared to the MYO group, thus indicating a more advanced progression of learning; ii) contextual demands degrade mental workload and cognitive-motor performance similarly in both prosthetic groups and; iv) the preliminary assessment of reliability and validity of the novel mental workload self-report measure shows promise for capturing changes in mental workload during cognitive-motor performance in a rehabilitation context. Although more research is warranted to confirm and extend the findings of this work to clinical upper-limb prosthesis users, this work has the potential to inform the cognitive-motor processes in this population and inform prescriptive decisions for patient device selection, prosthetic device design and rehabilitation program development.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.