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(1 - 20 of 26)
Pages
- Title
- Mechanosensitive reflex input from distal colon to neurons in pelvic plexus ganglia
- Creator
- Lin, Jingyang
- Date
- 1995
- Collection
- Electronic Theses & Dissertations
- Title
- Role of calcium-binding proteins and voltage-gated calcium channels in methymercury-induced disruption of divalent cation homeostasis and subsequent cytotoxicity
- Creator
- Edwards, Joshua R.
- Date
- 2004
- Collection
- Electronic Theses & Dissertations
- Title
- Local control of the axonal cytoskeleton
- Creator
- Baas, Peter William
- Date
- 1987
- Collection
- Electronic Theses & Dissertations
- Title
- Differential drug effects on dopaminergic neurons of the rat brain
- Creator
- Gudelsky, Gary A.
- Date
- 1977
- Collection
- Electronic Theses & Dissertations
- Title
- A study of the ultrastructure of the developing cuneate nucleus of pouch young opossums after early deafferentation
- Creator
- Ostapoff, Ernst-Michael
- Date
- 1980
- Collection
- Electronic Theses & Dissertations
- Title
- Morphological analysis of rat neostriatal neurons
- Creator
- Chang, Howard Tien-Haw
- Date
- 1981
- Collection
- Electronic Theses & Dissertations
- Title
- PC12 neurite outgrowth in the absence of microtubules on extracellular matrix
- Creator
- Steel, Vivian Lynn
- Date
- 1988
- Collection
- Electronic Theses & Dissertations
- Title
- Ultrastructural and HRP studies of regional variation and maturation of neurosecretory cells and glia of the goldfish preoptic area
- Creator
- Gregory, William A.
- Date
- 1982
- Collection
- Electronic Theses & Dissertations
- Title
- The role of parkin in the recovery of central dopamine neurons from acute neurotoxicant exposure
- Creator
- Benskey, Matthew John
- Date
- 2013
- Collection
- Electronic Theses & Dissertations
- Description
-
Parkinson Disease (PD) pathology is associated with the selective degeneration of nigrostriatal dopamine (NSDA) neurons, while the tuberoinfundibular DA (TIDA) neurons of the hypothalamus remain intact. The same pattern of selective degeneration has been observed following exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyradine (MPTP), a mitochondrial complex I inhibitor which recapitulates many of the molecular pathologies associated with PD. The purpose of this dissertation is to...
Show moreParkinson Disease (PD) pathology is associated with the selective degeneration of nigrostriatal dopamine (NSDA) neurons, while the tuberoinfundibular DA (TIDA) neurons of the hypothalamus remain intact. The same pattern of selective degeneration has been observed following exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyradine (MPTP), a mitochondrial complex I inhibitor which recapitulates many of the molecular pathologies associated with PD. The purpose of this dissertation is to identify early molecular events that underlie TIDA neuron recovery from toxicant exposure and adapt these mechanisms in an attempt to rescue NSDA neurons from toxicity. NSDA neurons show loss of axon terminal DA concentrations following acute (20mg/kg; s.c.) and chronic (10 x 20mg/kg; s.c. over 35 days) MPTP administration and exhibit cell death following chronic MPTP administration. In contrast, TIDA neurons show no loss of axon terminal DA concentrations or cell death following acute or chronic MPTP exposure. The recovery of TIDA neurons is independent of extrinsic factors such as decreased toxicant exposure or hormonal activation. TIDA neuron recovery is associated with an increase in the PD-associated proteins, parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL-1) within the arcuate nucleus (ARC) 24 h following MPTP. Additionally, parkin protein concentrations remain elevated in the ARC for up to 22 days following chronic MPTP administration. In contrast, the susceptibility of NSDA neurons is associated with decreased expression of both parkin and UCH-L1. The high correlation between the presence of the parkin protein and the recovery of DA neurons from MPTP toxicity is consistent with a role of parkin in DA neuron survival. In order to determine if parkin is necessary and sufficient in the recovery of TIDA neurons following MPTP, recombinant adeno-associated viral (rAAV) vectors containing parkin shRNA or a scrambled shRNA were created. Mice received stereotaxic ARC injections of rAAV containing either parkin shRNA or scrambled shRNA (250nl/side; 3.5x1013vg/ml), or remained naïve to surgery, and were administered a single injection of MPTP (20mg/kg; s.c.) 30 days following rAAV surgery. Twenty-four h post-MPTP, TIDA neurons were able to recover axon terminal DA concentrations following MPTP in control and scrambled shRNA treated animals. However, axon terminal DA was significantly reduced 24 hr following MPTP exposure following knockdown of parkin in TIDA neurons. To determine if parkin overexpression would protect NSDA neurons from MPTP toxicity, mice received unilateral stereotaxic injection of rAAV containing parkin into the substantia nigra (SN) (500nl; 3.4x1013vg/ml) and were administered a single injection of MPTP (20mg/kg; s.c.) 30 days following rAAV surgery. Twenty-four hours post-MPTP, parkin overexpression was unable to rescue MPTP-induced loss of DA in the striatum (ST), but did rescue MPTP-induced loss of tyrosine hydroxylase (TH) in the SN and ST. These findings are consistent with the following conclusions: 1) TIDA neuronal recovery from acute MPTP exposure is independent of extrinsic factors and is mediated by an intrinsic ability to increase expression of neuroprotective proteins, 2) The ability of TIDA neurons to up-regulate parkin is at least partially responsible for recovery of axon terminal DA following MPTP, 3) toxicant-induced loss of parkin contributes to MPTP toxicity within NSDA neurons.
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- Title
- Graph-based methods for inferring neuronal connectivity from spike train ensembles
- Creator
- El-dawlatly, Seif El-din
- Date
- 2011
- Collection
- Electronic Theses & Dissertations
- Description
-
Understanding the brain's inner workings requires studying the underlying complex networks that bind its basic computational elements, the neurons. Advances in extracellular neural recording techniques have enabled simultaneous recording of spike trains from multiple single neurons in awake, behaving subjects. Yet, devising methods to infer connectivity among these neurons has been significantly lacking. We introduce a connectivity inference framework based on graphical models. We first infer...
Show moreUnderstanding the brain's inner workings requires studying the underlying complex networks that bind its basic computational elements, the neurons. Advances in extracellular neural recording techniques have enabled simultaneous recording of spike trains from multiple single neurons in awake, behaving subjects. Yet, devising methods to infer connectivity among these neurons has been significantly lacking. We introduce a connectivity inference framework based on graphical models. We first infer the functional connectivity between neurons by searching for clusters of statistically dependent spike trains. We then infer the effective connectivity between neurons within each cluster by building Dynamic Bayesian Network (DBN) model fit to the spike train data. Using probabilistic models of neuronal firing, we demonstrate the utility of this framework to infer neuronal connectivity in moderate and large scale networks with a substantial gain in performance compared to classical methods. We further use this framework to examine the role of spike timing correlation in infragranular layer V of the primary somatosensory cortex (S1) of the rat during unilateral whisker stimulation in vivo. Stable, whisker-specific networks provided more information about the stimulus than individual neurons' response. We finally demonstrate how this framework enables tracking and quantifying plastic changes in connectivity in biologically-plausible models of spike-timing-dependent-plasticity as well as changes in S1 response maps following sensory deprivation in the awake, behaving rat.
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- Title
- Morphologic changes in preganglionic sympathetic neurons of rat following exercise and aging
- Creator
- Dey, Richard Dennis
- Date
- 1975
- Collection
- Electronic Theses & Dissertations
- Title
- Outward potassium currents of supraoptic magnocellular neurosecretory cells isolated from the adult guinea pig
- Creator
- Hlubek, Michael David
- Date
- 1997
- Collection
- Electronic Theses & Dissertations
- Title
- Relationship between methylmercury-induced disruption of intracellular calcium and neuronal death
- Creator
- Limke, Tobi Leigh
- Date
- 2001
- Collection
- Electronic Theses & Dissertations
- Title
- Statistical signal processing tools for analyzing large-scale neural ensembles
- Creator
- Aghagolzadeh, Mehdi
- Date
- 2012
- Collection
- Electronic Theses & Dissertations
- Description
-
Understanding how a neuron processes information and communicates with other neurons is key to unravel the brain's mechanisms underlying perception, learning and motor processing. Key to characterize neurons acting in concert is the ability to simultaneously measure their firing patterns in awake behaving subjects. Microelectrode arrays (MEAs) implanted in the brain allow simultaneous monitoring of the activity of large ensembles of cells while subjects carry out specific tasks. Isolating the...
Show moreUnderstanding how a neuron processes information and communicates with other neurons is key to unravel the brain's mechanisms underlying perception, learning and motor processing. Key to characterize neurons acting in concert is the ability to simultaneously measure their firing patterns in awake behaving subjects. Microelectrode arrays (MEAs) implanted in the brain allow simultaneous monitoring of the activity of large ensembles of cells while subjects carry out specific tasks. Isolating the spike pattern characterizing each cell's signature firing requires sophisticated signal processing algorithms, particularly to track the nonstationary behavior of these waveforms over extended periods of time. In this thesis, we introduce a compressive spike sorting technique that discriminates spike patterns from individual neurons using a sparse representation of the ensemble raw data. An iterative learning algorithm is introduced to estimate and adapt a set of optimal thresholds that maximize the separability between spike classes while minimizing the average waveform reconstruction error. Once derived, spike trains are then used to infer functional connectivity patterns among the recorded neural ensemble constituents. We introduce two information-theoretic approaches within the realm of graphical models that capture the spatiotemporal dependency between neurons' spiking patterns. Specifically, the class of spatiotemporal maximum entropy models is shown to incorporate higher-order interactions. We demonstrate the richness of these techniques in improving our understanding of neural function and dysfunction at the millisecond and micron resolutions, and their potential to be applied in emerging applications of brain machine interface technology to help improve the lifestyle of people with severe disabilities.
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- Title
- Organization of projection neurons in the rat hypothalamic paraventricular nucleus
- Creator
- Armstrong, William Earl
- Date
- 1979
- Collection
- Electronic Theses & Dissertations
- Title
- The role of lateral hypothalamic neurotensin neurons in adaptive energy balance
- Creator
- Brown, Juliette Anne
- Date
- 2017
- Collection
- Electronic Theses & Dissertations
- Description
-
The lateral hypothalamic area (LHA), receives cues of energy and fluid status from the body and coordinates appropriate feeding, drinking and activity (e.g. adaptive responses) to ensure survival. The LHA contains many distinct populations of neurons, however, and it remains unclear how each of these contribute to energy balance. Here we sought to understand how LHA neurons expressing the neuropeptide neurotensin (LHA Nts neurons) coordinate distinct behaviors necessary for adaptive response...
Show moreThe lateral hypothalamic area (LHA), receives cues of energy and fluid status from the body and coordinates appropriate feeding, drinking and activity (e.g. adaptive responses) to ensure survival. The LHA contains many distinct populations of neurons, however, and it remains unclear how each of these contribute to energy balance. Here we sought to understand how LHA neurons expressing the neuropeptide neurotensin (LHA Nts neurons) coordinate distinct behaviors necessary for adaptive response and control of body weight. While activation of most LHA Neurons increases both feeding and drinking, activation of LHA Nts neurons specifically promotes drinking but reduces feeding. LHA Nts neurons may exert these divergent actions via distinct circuits, as they have been shown to modulate dopamine (DA) signaling and local orexin (OX) neurons. Consistent with this, we have distinguished two projection-specific and molecularly distinct subsets of LHA Nts neurons. One subset co-expresses Nts and the long form of the leptin receptor (LepRb), is activated by leptin and projects to the ventral tegmental area (VTA) and substantia nigra compacta (SNc); we refer to these as NtsLepRb neurons. A separate subset of LHA Nts neurons lacks LepRb, is activated by dehydration and does not project to the VTA or SNc; we refer to these as Nts Dehy neurons. Intriguingly, however, we found all LHA Nts neurons are similar in that they express the inhibitory neurotransmitter, GABA. We next investigated the role of the NtsLepRb subpopulation for adaptive response by studying mice lacking leptin signaling via Nts LepRb neurons. Loss of leptin regulation only via NtsLepRb neurons induced obesity, blunted adaptive response to leptin and to ghrelin (a hormonal activator of OX neurons) and dysregulated DA signaling. Finally, we defined the necessity of LHA Nts neurons for energy balance by genetically ablating or chemogenetically inhibiting them in adult mice. Prolonged loss of LHA Nts neurons decreased drinking, locomotor activity and deranged OX expression in target neurons that led to increased adiposity. By contrast, LHA Nts inhibition preserved OX expression but still blunted locomotor activity. Together these data suggest that LHA Nts neurons modulate physical activity that is not dependent on OX, but that the LHA Nts→OX circuit is necessary for regulation of drinking and adiposity. Collectively, our data show that LHA Nts neurons are necessary for regulation of adaptive energy balance, and that distinct subpopulations of LHA Nts neurons may control ingestive and locomotor behavior via OX-dependent and independent pathways. This work suggests that there may be unique LHA Nts circuits to regulate drinking, motivated feeding ingestive disorders such as obesity, anorexia nervosa, psychogenic polydipsia and dehydration.
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- Title
- Transcriptional regulation of brain-derived neurotrophic factor in neurons
- Creator
- Zheng, Fei
- Date
- 2011
- Collection
- Electronic Theses & Dissertations
- Description
-
Neuroplasticity is an important feature of mammalian brains, referring to the functional or structural changes of the nervous system after learning or adapting to the changes of environment. Activity-dependent transcription is critical for neuroplasticity. Brain-derived neurotrophic factor, an activity-dependent gene, has emerged as a key molecule in synaptic plasticity, memory formation and neurological diseases. The regulation of activity-dependent BDNF transcription remains elusive.Exon IV...
Show moreNeuroplasticity is an important feature of mammalian brains, referring to the functional or structural changes of the nervous system after learning or adapting to the changes of environment. Activity-dependent transcription is critical for neuroplasticity. Brain-derived neurotrophic factor, an activity-dependent gene, has emerged as a key molecule in synaptic plasticity, memory formation and neurological diseases. The regulation of activity-dependent BDNF transcription remains elusive.Exon IV-containing BDNF mRNA (BDNF IV) is one of the major activity-responsive forms of the multiple BDNF mRNAs. Calcium influx via calcium channel or NMDA receptor stimulates BDNF IV transcription in cortical neurons, which requires activity of MAPK, PI3K, PKA and CaMKs. The three identified calcium-responsive elements (CaREs) in the BDNF IV promoter (promoter IV) mediate calcium-induced BDNF IV transcription coordinately. In mature neurons, only CaRE1 and CaRE3 are responsive to calcium influx and are regulated by MAPK, PI3K and CaMKs in a stimulation-selective manner.BDNF IV is also induced by self-stimulation, which is regulated by MAPK activity, extra- and intracellular calcium level and the NMDA receptor. Both NR2A-and NR2B-containing NMDA receptors, as well as synaptic and extrasynaptic NMDA receptor, are required for BDNF self-induction. Moreover, a synergistic effect of BDNF and NMDA stimulation has been found for BDNF IV upregulation.In summary, we suggest a novel working model for the regulation of calcium- and BDNF-induced BDNF transcription.
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- Title
- Regulation of tuberohypophyseal dopaminergic neurons
- Creator
- Alper, Richard H.
- Date
- 1981
- Collection
- Electronic Theses & Dissertations
- Title
- Effects of methylmercury on cerebellar granule cells of the tottering mouse
- Creator
- Marrero-Rosado, Brenda Marie
- Date
- 2013
- Collection
- Electronic Theses & Dissertations
- Description
-
Methylmercury (MeHg) is an organic highly toxic form of mercury and a persistent environmental neurotoxicant. The most common manner in which humans are exposed to MeHg is by consumption of contaminated fish. Studies from cases of chronic and acute human poisonings have revealed that MeHg causes a massive loss of cerebellar granule cells (CGCs), causing the characteristic dysarthria and ataxic signs. Previous research has found that acute treatment of rat CGCs with MeHg
in vitro<... Methylmercury (MeHg) is an organic highly toxic form of mercury and a persistent environmental neurotoxicant. The most common manner in which humans are exposed to MeHg is by consumption of contaminated fish. Studies from cases of chronic and acute human poisonings have revealed that MeHg causes a massive loss of cerebellar granule cells (CGCs), causing the characteristic dysarthria and ataxic signs. Previous research has found that acute treatment of rat CGCs with MeHg
Show morein vitro causes a time- and concentration-dependent increase in intracellular Ca2+ ([Ca2+ ]i) that is sufficient to cause CGC death. Voltage-gated Ca2+ channels (VGCCs) are believed to play a role in the mechanism of MeHg-induced cytotoxicity by possibly facilitating access for the metal to intracellular targets. Many subtypes of VGCCs are expressed in CGCs, each characterized by different pharmacological and kinetic properties. The endeavor of the present studies was to investigate the effects of MeHg on CGCs of a mouse model of human Cav2.1 (P/Q-type) channelopathy. Thetottering (tg ) mouse is the result of a non-lethal deleterious point mutation in the á1A pore-forming subunit of the P/Q-type Ca2+ channel. This VGCC subtype plays a crucial role in the process of neurotransmitter release in mature CGCs of humans and animal models. Data will show that, in low-K+ conditions (closely mimicking their mature state) CGCs isolated from mice homozygous (tg/tg ) and heterozygous (+/tg ) for thetg mutation present a delay in the onset of MeHg-induced [Ca2+ ]i increasein vitro . On the other hand, when they are acutely exposed to MeHg under depolarizing environments (mimicking their state in early development)tg/tg CGCs show increased susceptibility to cytotoxicity. Cerebellar organotypic slices from postnatal day (PND) 23-25 (after onset of ataxia) mice were also used to study the response of CGCs to MeHg taking into account the entire local cerebellar circuitry. Interestingly, +/tg cerebellar organotypic slices showed a higher percentage of CGC death thanWT andtg/tg . The effect of MeHg on +/tg CGCs was partially eliminated by pretreating the slices with ù-conotoxin GVIA, an N-type VGCC antagonist. This suggests an important role of N-type VGCCs in the greater susceptibility of mature +/tg CGCs to MeHg. Of great importance is thattg -like mutations have been linked to human disorders including episodic ataxia type 2, familial hemiplegic migraine and spinocerebellar ataxia type 6. This work presents evidence of a genotype-environment interaction that could potentially identify human populations with higher risk for the neurotoxic effects of MeHg.
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- Title
- Effects of deafferentation of three identified neurons in the last abdominal ganglion of the cockroach, Periplaneta americana (Orthoptera)
- Creator
- Tipton, Virginia Martin, 1943-
- Date
- 1976
- Collection
- Electronic Theses & Dissertations