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Medial Medulla Networks in Culture: a Multichannel Electrophysiologic and Pharmacological StudyKeefer, Edward W. (Edward Wesley) 08 1900 (has links)
Spontaneously active primary cultures obtained from dissociated embryonic medial medulla tissue were grown on microelectrode arrays for investigating burst patterns and pharmacological responses of respiratory-related neurons. Multichannel burst rates and spike production were used as primary variables for analysis. Pacemaker-like neurons were identified by continued spiking under low Ca++/high Mg++conditions. The number of pacemakers increased with time under synaptic blocking medium. Sensitivity to CO2 levels was found in some neurons. Acetylcholine changed activity in a complex fashion. Curare, atropine and gallamine modified ACh effects. Eserine alone was ineffective, but potentiated ACh-induced responses. Norepinephrine caused channel-specific increases or decreases, whereas dopamine and serotonin had little effect at 30 μM. GABA and glycine stopped most spiking at 70 μM. Developmental changes in glycine sensitivity (increasing with age) were also observed. It is concluded that pacemaker and chemosensitive neurons develop in medial medulla cultures, and that these cultures are pharmacologically histiotypic.
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Levels of PARP1-immunoreactivity in the Human Brain in Major Depressive DisorderShaikh, Aamir 01 May 2020 (has links)
MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search for other pathologies in depression that might yield clues for the development of better drug treatments. In this regard, a strong association has been found between oxidative stress and MDD. Our lab recently found increased DNA oxidation and elevated poly(ADP)ribose polymerase (PARP1) gene expression in the brain from donors that had MDD at the time of death. Besides DNA damage repair, PARP1 mediates several downstream inflammatory effects that may contribute to pathology in MDD. In fact, our lab has demonstrated that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as a novel antidepressant drug. While our lab had previously demonstrated elevated PARP1 gene expression in the frontal cortex in MDD, whether PARP1 protein levels were also increased in depression had not been verified. My thesis research was performed to determine whether PARP1 protein expression was also elevated in the brain in MDD. I studied primarily the hippocampus because it is part of the limbic (mediating emotion) system of the brain and because previous research has shown numerous other pathologies in the hippocampus. My study was carried out simultaneously as others in our lab were measuring PARP1 protein levels in frontal cortex in MDD. This latter work was important since the lab’s previous work had observed elevated PARP1 gene expression in the frontal cortex, rather than in the hippocampus which was not previously studied. Hippocampal and frontal cortical brain sections were cut from frozen blocks of both MDD and psychiatrically normal control brain donors for these studies. PARP1 protein levels were estimated by assisted-imaging software. The findings herein demonstrate that levels of PARP1 immunoreactivity are significantly elevated in the frontal cortex of MDD donors as compared to control donors. However, there was no change in PARP1 immunoreactivity in the hippocampus in MDD.
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Exploration of hierarchical leadership and connectivity in neural networks in vitro.Ham, Michael I. 12 1900 (has links)
Living neural networks are capable of processing information much faster than a modern computer, despite running at significantly lower clock speeds. Therefore, understanding the mechanisms neural networks utilize is an issue of substantial importance. Neuronal interaction dynamics were studied using histiotypic networks growing on microelectrode arrays in vitro. Hierarchical relationships were explored using bursting (when many neurons fire in a short time frame) dynamics, pairwise neuronal activation, and information theoretic measures. Together, these methods reveal that global network activity results from ignition by a small group of burst leader neurons, which form a primary circuit that is responsible for initiating most network-wide burst events. Phase delays between leaders and followers reveal information about the nature of the connection between the two. Physical distance from a burst leader appears to be an important factor in follower response dynamics. Information theory reveals that mutual information between neuronal pairs is also a function of physical distance. Activation relationships in developing networks were studied and plating density was found to play an important role in network connectivity development. These measures provide unique views of network connectivity and hierarchical relationship in vitro which should be included in biologically meaningful models of neural networks.
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TIR-1/SARM1 Inhibits Axon RegenerationJulian, Victoria L. 01 September 2021 (has links)
The inability to repair axonal damage is a feature of neurological impairment after injury and in neurodegenerative diseases. Axonal repair after injury depends in part on intrinsic factors. Several genes cell-autonomously regulate both axon regeneration and degeneration in response to injury. Recently, Sarm1 has emerged as a key regulator of neurodegeneration. Whether Sarm1 plays a role in axon regeneration is unknown. In this thesis, I identified a role for the C. elegans homolog of Sarm1, tir-1, as a negative regulator of axon regeneration.
Investigating the genes which regulate axon regeneration and degeneration has been hindered by technical difficulties in visualizing and manipulating both of these processes in vivo simultaneously. To circumvent this challenge, I developed a new model of axon injury, where both axon regeneration and degeneration can be monitored in vivo with single neuron resolution in C. elegans. I found that the C. elegans homolog of Sarm1, tir-1, strongly inhibits axon regeneration in response to injury. I found that TIR-1 functions cell-intrinsically and that its subcellular localization is dynamically regulated in response to injury. To regulate both axon regeneration and degeneration after injury, I found that TIR-1 function is determined by interaction with two distinct genetic pathways. Together, this work reveals a novel role for tir-1/Sarm1 in axon regeneration, increases our understanding of the injury response, provides new avenues of investigation for studies of TIR-1/SARM1, and inspires candidate approaches to repair the injured nervous system.
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Ontogenetic and Adult Shape Variation in the Endocast of Tapirus: Implications for T. polkensis from the Gray Fossil SiteGaetano, Thomas M 01 May 2020 (has links)
Endocranial morphology provides evidence of sensory ecology and sociality of extinct vertebrates. The Earliest Pliocene Gray Fossil Site (GFS) of NE Tennessee features a conspicuous dominance of skeletal elements belonging to the dwarf tapir, Tapirus polkensis. Numerous individuals in one fossil locality often suggests gregarious behavior, but sociality in T. polkensis contradicts behavior documented for extant Tapirus species. I test T. polkensis for variation in sensory and social ecology using computed tomography and 3D digital endocasts from an ontogenetic sequence. I compare the T. polkensis endocasts with extant Tapirus species using Encephalization Quotients (EQs) and 3D geometric morphometrics. Results show conserved endocast morphology for Tapirus, and thus, conserved sensory and social ecology. Tapirus behavior is likely consistent for ~5 Ma, and extant Tapirus behavior can be inferred for T. polkensis. The large number of individuals from the GFS is likely the result of a preservation bias unrelated to gregariousness.
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Acute Effects of the Antibiotic Streptomycin on Neural Network Activity and Pharmacological ResponsesZeng, Wei Rong 12 1900 (has links)
The purpose of this study is to find out that if antibiotic streptomycin decreases neuronal network activity or affects the pharmacological responses. The experiments in this study were conducted via MEA (multi-electrode array) technology which records neuronal activity from devices that have multiple small electrodes, serve as neural interfaces connecting neurons to electronic circuitry. The result of this study shows that streptomycin lowered the spike production of neuronal network, and also, sensitization was seen when neuronal network pre-exposed to streptomycin.
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An investigation of female house mosquito (Culex pipiens) photo responses to male flashing wingbeat frequencyStec, Helen 28 April 2022 (has links)
No description available.
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The effects of delta-9 tetrahydrocannabinol (THC) on responding for non-drug reinforcers in rats.Radford, Anna 01 May 2022 (has links)
Although cannabis is widely consumed by humans for the intoxicating effects that are mediated by delta-9 tetrahydrocannabinol (THC), pre-clinical models of THC self-administration have been difficult to establish. We hypothesized that THC may have reinforcement enhancing effects comparable to other drugs (e.g., nicotine and caffeine), which are also widely consumed by humans but difficult to establish as primary reinforcers in non-human animals. To investigate whether THC is a reinforcement enhancer, male (M, n=8) and female (F, n=8) rats were shaped to self-administer a reinforcing saccharin (SACC) solution (0.2% w/v) in standard operant chambers equipped with infrared beams to monitor locomotor activity. At baseline, we found a significant sex difference for active lever responses and reinforcers earned (F
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Neurochemical Status and Cortical Oscillatory Activity in aGenetic Mouse ModelKlocke, Benjamin 20 August 2020 (has links)
No description available.
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Temporal Organization of Behavioral States through Local Neuromodulation in C. elegansBanerjee, Navonil 14 December 2016 (has links)
Neuropeptide signaling play critical roles in maintaining distinct behavioral states and orchestrating transitions between them. However, elucidating the mechanisms underlying neuropeptide modulation of neural circuits in vivo remains a major challenge. The nematode Caenorhabditis elegans serves as an excellent model organism to study neuropeptide signaling mechanisms encoded in relatively simple neural circuits. We have used the C. elegans egg-laying circuit as a model to understand how neuropeptide signaling modifies circuit activity to generate opposing behavioral outcomes. C. elegans egg-laying behavior is composed of alternating cycles of two states – short bursts of egg deposition (active phases) and prolonged periods of quiescence (inactive phases). We have identified two neuropeptides (NLP-7 and FLP-11) that are locally released from a group of neurosecretory cells (uv1) and coordinate the temporal organization of egglaying by prolonging the duration of inactive phases. These neuropeptides regulate activity within the core circuit by inhibiting serotonergic transmission between its individual components (HSN motorneurons and Vm2 vulval muscles). This inhibition is achieved at least in part, by reducing synaptic vesicle abundance in the HSN synaptic regions. To identify potential downstream signaling components that mediate the actions of these neuropeptides, we have performed a forward genetic screen and have identified a strong candidate. In addition, we are trying to identify the receptor(s) of these neuropeptides by using a candidate gene approach. Together, we demonstrate that local neuropeptide signaling maintains the periodicity of distinct behavioral states by regulating serotonergic transmission in the core neural circuit.
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