Biology
Permanent URI for this communityhttp://hdl.handle.net/1903/11810
Browse
16 results
Search Results
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 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 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 PHYSIOLOGICAL CHARACTERIZATION OF SPECIFIC LOCAL INTERNEURON SUBPOPULATIONS IN THE DROSOPHILA ANTENNAL LOBE(2022) Schenk, Jonathan Edward; Gaudry, Quentin; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The olfactory system of the fruit fly Drosophila melanogaster is an invaluable model for understanding circuit function. Composed mainly of olfactory receptor neurons (ORNs), projection neurons (PNs), and local interneurons (LNs), it is an analogous structure to mammalian olfactory systems. Of these cell types, LNs are particularly intriguing. These neurons are found in a variety of morphologies and with differing neurotransmitter and receptor profiles. Given their heterogeneity, it is critical to gain an understanding of their roles in olfactory circuits. In this work, I probe the physiology and functions of two unique subpopulations of LNs in the antennal lobe (AL). In the first population, I demonstrate LNs which respond to extrasynaptic, paracrine levels of serotonergic modulation. These LNs then engage in postsynaptic inhibition and subtractive gain control, which is contrary to typical LNs. The second population I characterize are previously undescribed nonspiking LNs in the fly AL. Nonspiking cells are common to insect olfaction as well as other sensory pathways in vertebrates. I find that these neurons are likely to be electrotonically compartmentalized, such that activation within individual regions does not propagate across the whole cell, suggesting roles in previously unexplained mechanisms such as intraglomerular inhibition. The results of this work suggest more heterogeneity in Drosophila LNs than previously assumed and cements the importance of interneuron contribution to neuronal function.Item Regulation of Endocytosis at Mammalian Central Synapses(2022) Shi, Bo; Wu, Ling-Gang; Pick, Leslie; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Synaptic endocytosis retrieves exocytosed vesicles and maintains synaptic transmission which is essential to neural circuit functions. Accumulated studies suggest that calcium influx triggers synaptic vesicle endocytosis, which must undergo membrane pit formation and fission of the pit’s neck to generate vesicles. However, the calcium sensor that links calcium to endocytic machinery remains not well understood; whether pit formation involves clathrin remains debated, what mechanism controls the endocytic vesicle size remains not well understood either; the mechanism that couples exo- to endocytosis remains not fully understood either. My thesis work aims at improving our understanding of each of these questions. I studied endocytosis using a combination of techniques, including gene knockout, gene knockdown, fluorescence imaging, electron microscopy, and molecular biology techniques. I identified the calcium sensors that link calcium influx to endocytosis – the protein kinase C α and β isoforms and calmodulin. I found that clathrin is involved in mediating endocytosis at synapses, which may clarify the doubts on whether clathrin is indispensable for synaptic vesicle endocytosis. I found that dynamin is crucial not only for fission as generally thought, but also for controlling the vesicle size at hippocampal synapses, which enhances our understanding on how vesicle size is regulated at synapses. I found that NSF, which disassembles the SNARE complex, is crucial for mediating synaptic vesicle endocytosis, which enhance our understanding of the mechanisms that couple exo- to endocytosis. Consequently, In summary, I identified endocytosis calcium sensor as protein kinase C (α and β isoforms) and calmodulin; found clathrin in playing a role in pit formation, discovered a novel function of dynamin in controlling vesicle size, and reveal NSF in coupling exo- to endocytosis. These findings contribute to better understanding regulation of endocytosis at synapses.Item THE ROLE OF THE VENTRAL STRIATUM AND AMYGDALA IN REINFORCEMENT LEARNING(2021) Taswell, Craig Anthony; Butts , Daniel; Averbeck , Bruno; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Adaptive behavior requires that organisms choose wisely to gain rewards and avoid punishment. Reinforcement learning refers to the behavioral process of learning about the value of choices, based on previous choice outcomes. From an algorithmic point of view, rewards and punishments exist on opposite sides of a single value axis. However, simple distinctions between rewards and punishments and their theoretical expression on a single value axis hide considerable psychological complexities that underlie appetitive and aversive reinforcement learning. A broad set of neural circuits, including the amygdala and frontal-striatal systems, have been implicated in mediating learning from gains and losses. The ventral striatum (VS) and amygdala have been implicated in several aspects of this process. To examine the role of the VS and amygdala in learning from gains and losses, we compared the performance of macaque monkeys with VS lesions, with amygdala lesions, and un-operated controls on a series of reinforcement learning tasks. In these tasks monkeys gained or lost tokens, which were periodically cashed out for juice, as outcomes for choices. We found that monkeys with VS lesions had a deficit in learning to choose between cues that differed in reward magnitude. Monkeys with VS lesions performed as well as controls when choices involved a potential loss. In contrast, we found that monkeys with amygdala lesions performed as well as controls across all conditions. Further analysis revealed that the deficits we found in monkeys with VS lesions resulted from a reduction in motivation, rather than the monkeys’ inability to learn the stimulus-outcome contingency.Item Extratympanic hearing in salamanders: A comparative assessment of structural variation and terrestrial function of an atympanic ear(2021) Capshaw, Grace; Carr, Catherine E; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The auditory system mediates the detection of acoustic cues and enhances survival within complex environments by enabling organisms to construct an auditory scene of their surroundings. The tympanic middle ear evolved multiple times in all terrestrial tetrapod lineages to overcome the impedance mismatch encountered by sound pressure at the air-skin boundary, indicating its significance for aerial hearing; however, fossil evidence demonstrates that the earliest terrestrial tetrapods retained aquatically-adapted ears that were unspecialized for detecting airborne sound. How did these unspecialized ears function on land? Comparative study of extant atympanate vertebrates can provide key insights into the ancestral state and early evolution of the terrestrial tetrapod auditory system following the water-to-land transition. In this dissertation, I use atympanate salamanders as a model to investigate the structural and functional parameters underlying terrestrial hearing with unspecialized ears. In chapter one, I review the biology of the salamander auditory system. In chapter two, I characterized morphological variation of the salamander ear and found evidence for habitat-related specialization, suggesting underlying physiological variation. In chapter three, I measured auditory sensitivity to sound pressure and seismic vibration, and observed variation in sensitivity that corroborates the ecomorphological trends reported in chapter two. I assessed the contributions of hypothesized extratympanic pathways for hearing, including seismic sensitivity, cavity resonance, and bone conduction. I determined that aerial auditory sensitivity is mediated by bone conduction of sound as head vibrations that are detectable to the inner ear. In chapter four, I evaluated the sound localization capabilities of an atympanic ear. I found that bone conduction hearing in salamanders supports a figure-eight pattern of directional sensitivity to airborne sound. I contextualize my findings with other studies of tympanate and atympanate taxa and suggest that bone conduction may represent a general mechanism enabling aerial sound detection and localization in terrestrial species with atympanic ears.Item EARLY CHRONIC MONOCULAR VISUAL DEPRIVATION COMPROMISES THE RETINAL FUNCTION OF THE DEPRIVED EYE(2020) Ara, Jawshan; Quinlan, Elizabeth M.; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Amblyopia is caused by abnormal visual experience during early childhood such as unilateral cataract, strabismus, and anisometropia. The misalignment of the images in the case of strabismus or blurriness/haziness of the image quality originating from the defective eye results in reduced visual acuity and contrast sensitivity in the deprived eye (Volkers et al., 1987) in comparison to the non-deprived eye and limits stereopsis in humans (Husk et al., 2012). Most clinical treatments for amblyopia penalize the fellow eye to bias the visual system towards the input from the amblyopic eye. Unfortunately, current clinical treatments for amblyopia are most effective in children younger than 7 years old (Cotter et al., 2012). Works in animal models of amblyopia are beginning to identify ways to improve vision in adult amblyopes. They have focused almost exclusively on deficits in the functions of the visual cortex. However, dark rearing can reduce the amplitude of the photopic Electroretinogram indicating reduced functions of cone-mediated retinal functions and alter the mGluR6 distribution and intensity in the first synapses between cone photoreceptors and ON bipolar cells (Dunn et al., 2013). It is predicted but not yet tested, that monocular deprivation will have a similar impact on retinal functions. Here we characterize various aspects of the effect of chronic monocular deprivation (cMD) on retinal functions in adult mice. We observed that chronic monocular deprivation significantly reduced electroretinogram (ERG) response originating from the inner retinal plexiform layer of the deprived eye retina in comparison to the non-deprived eye retina. Our observation suggests that early chronic visual deprivation compromises the retinal function of the deprived eye of the adult mice.Item SOCIAL AND ECOLOGICAL FACTORS INFLUENCING COLLECTIVE BEHAVIOR IN GIANT DANIO(2016) Chicoli, Amanda; Paley, Derek A; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)A fundamental problem in biology is understanding how and why things group together. Collective behavior is observed on all organismic levels - from cells and slime molds, to swarms of insects, flocks of birds, and schooling fish, and in mammals, including humans. The long-term goal of this research is to understand the functions and mechanisms underlying collective behavior in groups. This dissertation focuses on shoaling (aggregating) fish. Shoaling behaviors in fish confer foraging and anti-predator benefits through social cues from other individuals in the group. However, it is not fully understood what information individuals receive from one another or how this information is propagated throughout a group. It is also not fully understood how the environmental conditions and perturbations affect group behaviors. The specific research objective of this dissertation is to gain a better understanding of how certain social and environmental factors affect group behaviors in fish. I focus on two ecologically relevant decision-making behaviors: (i) rheotaxis, or orientation with respect to a flow, and (ii) startle response, a rapid response to a perceived threat. By integrating behavioral and engineering paradigms, I detail specifics of behavior in giant danio Devario aequipinnatus (McClelland 1893), and numerically analyze mathematical models that may be extended to group behavior for fish in general, and potentially other groups of animals as well. These models that predict behavior data, as well as generate additional, testable hypotheses. One of the primary goals of neuroethology is to study an organism's behavior in the context of evolution and ecology. Here, I focus on studying ecologically relevant behaviors in giant danio in order to better understand collective behavior in fish. The experiments in this dissertation provide contributions to fish ecology, collective behavior, and biologically-inspired robotics.Item ADAPTIVE FLIGHT AND ECHOLOCATION BEHAVIOR IN BATS(2015) Falk, Ben; Moss, Cynthia F; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Bats use sonar to identify and localize objects as they fly and navigate in the dark. They actively adjust the timing, intensity, and frequency content of their sonar signals in response to task demands. They also control the directional characteristics of their sonar vocalizations with respect to objects in the environment. Bats demonstrate highly maneuverable and agile flight, producing high turn rates and abrupt changes in speed, as they travel through the air to capture insects and avoid obstacles. Bats face the challenge of coordinating flight kinematics with sonar behavior, as they adapt to meet the varied demands of their environment. This thesis includes three studies, one on the comparison of flight and echolocation behavior between an open space and a complex environment, one on the coordination of flight and echolocation behavior during climbing and turning, and one on the flight kinematic changes that occur under wind gust conditions. In the first study, we found that bats adapt the structure of the sonar signals, temporal patterning, and flight speed in response to a change in their environment. We also found that flight stereotypy developed over time in the more complex environment, but not to the extent expected from previous studies of non-foraging bats. We found that the sonar beam aim of the bats predicted flight turn rate, and that the relationship changed as the bats reacted to the obstacles. In the second study, we characterized the coordination of flight and sonar behavior as bats made a steep climb and sharp turns while they navigated a net obstacle. We found the coordinated production of sonar pulses with the wingbeat phase became altered during navigation of tight turns. In the third study, we found that bats adapt wing kinematics to perform under wind gust conditions. By characterizing flight and sonar behaviors in an insectivorous bat species, we find evidence for tight coordination of sensory and motor systems for obstacle navigation and insect capture. Through these studies, we learn about the mechanisms by which mammals and other organisms process sensory information to adapt their behaviors.