Browsing by Author "Syed, Naweed I."

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    A novel form of post-tetanic potentiation
    (2004) Prince, David John; Syed, Naweed I.
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    A novel role for cdk5 in the cell cycle
    (2008) Yang, Songhua; Lee, Ki-Young; Syed, Naweed I.
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    Designing a novel 3-D in-Vitro scaffold to define mechanisms underlying neuronal myelination
    (2018-11-28) Shahidi, Sahar; Syed, Naweed I.; Sanati Nezhad, Amir; Ousman, Shalina S.; Yusuf, Kamran
    All nervous system functions in animals require neuronal assembly during development and the ensuing communications between large networks of neurons, which are often difficult to monitor in the intact brain. As such, most labs around the globe have opted to use and explore in vitro model systems where neurons are generally grown on two-dimensional, plane glass substrates, which limit the ability to decipher fundamental understanding of the mechanisms underlying neuronal growth, polarity and synapse specificity. Most approaches used today employ 2-D models where neurons are cultured on the Poly-D-lysine (PDL) coated substrate which does not mimic the 3-D configuration of the intact mammalian brain – thus limiting a direct comparison between in vivo and in vitro conditions. Assessing cellular and molecular mechanisms of neuronal myelination are critical to determine how myelination and demyelination processes occur in vertebrate models so as to understand developmental and neurodegenerative diseases such as multiple sclerosis. However, there are no suitable in vitro models available to date whereby the process of axon myelination could be studied directly at the level of individual central and peripheral neurons. In contrast to PDL, collagen offers a 3-D structure in which neurons can be suspended in a 3-D configuration, allowing glia to gain access to axonal membrane to exhibit myelination. However, we still lack a reliable 3-D model where mechanisms of neuronal polarity and myelination could be studied at the level of individual peripheral and central neurons. In this study, I designed a 3D substrate comprising of a gelatin base hydrogel with tunable chemical mechanical properties. Using rat Dorsal Root Ganglia Cells (DRG) and their corresponding Schwann cells (SC), I compared and contrasted the effectiveness of GelMA with PDL and Collagen substrates and provide the first direct evidence that the former is more conducive to studying myelination than the later two. Moreover, I also demonstrate that both DRG growth and SC behavior on GelMA resembles to what is seen in vivo thus validating further the usefulness of this substrate for future studies.
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    Dopamine-mediated synaptic plasticity at lymnaea synapses
    (2010) Asselin Jarry, Louis-Pierre; Syed, Naweed I.
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    Dynamics of Neural Responses in the Mouse Auditory Cortex: Construction and Characterization of 3D Receptive Fields in Frequency, Intensity and Time Domains
    (2019-01-24) Qureshi, Farhad Ahmad; Yan, Jun; Eggermont, Jos J.; Syed, Naweed I.
    Neurons in the central auditory system exhibit non-linear responses to acoustic stimulation. Such non-linearities are usually illustrated by frequency tuning curves (FTC), spectrotemporal receptive field (STRF) and dynamic ranges. None of these methods provide a complete representation of the neural responses in frequency, intensity and timing domains. A novel tool is developed to create neuronal receptive field in all three domains (3D receptive field), i.e., neural response representation across all three domains. The primary auditory cortex is selected for this study as it is a core area of auditory information processing. The 3D receptive field or the intensity-stacked spectrotemporal receptive field (iSTRF) was demonstrated in three visualizations: volume rendering, surface rendering and 2D slicing. All the three visualizations enable the characterization and/or description of the neural responses to sound in a comprehensive fashion. The iSTRF provides novel information about neuronal response properties that could not be provided by previous methods. In this thesis, I analyzed and presented two novel findings. One was the intensity coding in spectrotemporal domains that illustrated frequency dependent intensity coding within the excitatory receptive area of the neuron. Another is the neuronal best response dynamics curve in frequency, intensity and time domains. A sound signal was defined based on this curve that could potentially be the fingerprint or ID of that particular neuron. The data presented in this thesis suggests that the iSTRF can be a powerful tool for auditory studies by providing novel and more detailed information on the responses of auditory neurons to sound. The iSTRF can widely be applicable to comparing different brain regions, examining auditory plasticity and evaluating the efficiency of different hearing related devices such as cochlear implants.
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    Epidermal growth factor-receptor induced synapse formation between lymnaea neurons
    (2007) Gagatek, Jessics; Syed, Naweed I.
    Trophic factors are well known for their role in cell proliferation, differentiation, survival, neurite outgrowth, and more recently, in synapse formation and synaptic plasticity (Hamakawa et al., 1999). Despite their well defined roles during development, relatively little is known about the underlying cellular and molecular mechanisms governing their actions. In this study, 1 investigated the precise role of the invertebrate trophic factor, Lymnaea epidermal growth factor (L-EGF) and its receptor, L-EGFR, in mediating excitatory synapse fonnation between identified neurons visceral dorsal 4 (VD4) and its postsynaptic partner left pedal dorsal 1 (LPeDl). The data presented here show that L-EGF mimics brain-derived conditioned medium's (CM) ability to promote excitatory synapse formation between specific synaptic partners. Through pharmacological and molecular perturbations of the L-EGFR, I further demonstrated that the L-EGF-induced effects on synapse fonnation are mediated through the L-EGFR. Vertebrate EGF and its structural homologue, transforming growth factor-a (TGF-a), also promoted excitatory synapse formation between identified Lymnaea neurons, and these effects also appeared to be mediated through the L-EGF receptor. The fact that only L­EGF or its vertebrate homologues could signal through the L-EGFR suggests that this receptor is highly specific and is conserved among both vertebrate and invertebrate species. The Lymnaea soma-soma model thus provides an unparalleled opportunity to elucidate further molecular mechanisms by which trophic factors affect synapse formation.
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    Identification and characterization of ryanodine receptors in lymnaea neurons
    (2007) Montgomery, Elisha Anne; Syed, Naweed I.
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    Mercury-induced toxicity of rat cortical neurons is mediated through N-Methyl-D-Aspartate receptors
    (BioMed Central Ltd., 2012-09-14) Xu, Fenglian; Farkas, Svetlana; Kortbeek, Simone; Chen, Lina; Zhang, Fangxiong; Zamponi, Gerald W.; Syed, Naweed I.
    Mercury is a well-known neurotoxin implicated in a wide range of neurological or psychiatric disorders including autism spectrum disorders, Alzheimer's disease, Parkinson's disease, epilepsy, depression, mood disorders and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate-mediated excitotoxicity, however, the underlying mechanisms remain poorly understood. Here, we examine the effects of various mercury concentrations (including pathological levels present in human plasma or cerebrospinal fluid) on cultured, rat cortical neurons.
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    New approaches to identifying critical components of the calcium triggered membrane fusion machinery
    (2010) Furber, Kendra Lee; Coorssen, Jens R.; Syed, Naweed I.
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    Optimizing Multi-Well Micro-Electrode Array (MW-MEA) Design to Study the Electrophysiology of Neurons
    (2020-07-27) Pishgar, Roofia Sara; Dalton, Colin; Syed, Naweed I.; Teskey, G. Campbell; Dunn, Jeff F.; Murari, Kartikeya; Chu, Angus; Frayne, Richard
    Microelectrode arrays (MEAs) have been widely utilized to measure and study neuronal activities, both in vitro and in vivo. The main focus of this study was to optimize the MEA design to improve the recording efficiency from a group of cells in an area to have a better understanding of what is happening over a larger network. This study included three phases: investigating the effectiveness of a preliminary version of multi-well MEA design with two electrode types featuring a different number of wells (5 and 6) and diameter of wells (15 and 20 μm); 2) optimization of the first design with the second version of multi-well MEA, featuring a wider range of diameters and number of wells on each electrode; 3) investigating the adaptability of rigid glass-based MW-MEAs to flexible substrates. The results of this study showed that electrodes with 6-wells had the ability to capture stronger signals occasionally, while electrodes with 5-wells could consistently record signals, albeit with less peak-to-peak amplitudes. It was found out that the effect of diameter and number of wells and their correlation (i.e., the open surface area of the electrode, A) on the signal to noise ratio (SNR) were significant and thus should all be regarded as important parameters when designing MEAs. Cell signal recording was performed on the second MEA design, using snail brain neurons. Snail brain neurons were used to limit the complexity of neuronal recordings and to be able to focus the analysis on the electrode characteristics. However, due to the COVID-19 related shutdown, the snail recording could not be pursued further in the lab. The study on the suitability of using flexible substrates instead of the traditional rigid glass substrate to make a flexible MEA (fMEA) showed oxidation, electrode degradation, and formation of residues in long-term mice cell plating. It indicated the incompatibility of the materials used with living cells. In parallel, a gold wire bonding process was attempted to create 3D microelectrodes on the fMEA. 3D-fMEA fabrication proved to be challenging due to several difficulties in the wire bonding process, used for converting the planar fMEA to 3D-fMEA. Thus, to further the study on the effectiveness of fMEA and 3D-fMEA, the choice of material and fabrication protocol of fMEA and 3D-fMEA needs further investigation.
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    Oxygen Sensing in Lymnaea: from Behaviour to Central Pattern Generators
    (2016-02-02) Janes, Tara Adele; Syed, Naweed I.; Goldberg, Jeff; Whelan, Patrick
    From invertebrates to humans, the regulation of cellular O2 levels within narrow physiological limits represents a significant challenge, but one that is necessary for survival. This essential task of O2 homeostasis is controlled by the nervous system so as to meet metabolic O2 demands in the face of ever-changing environments or injury/disease. The process by which the nervous system exercises such precise control over systemic O2 levels is termed respiratory behaviour. Specialized neural circuits termed respiratory central pattern generators (rCPG’s) produce the basic rhythmic motor output underlying respiratory behaviour. In turn, rCPG activity is subject to extensive neuromodulation, which allows respiratory behaviour to be adapted to changing environments or during various disease states. However, the fundamental mechanisms by which rCPG networks collect and integrate sensory information about the O2 environment and orchestrate a diversity of adaptive behavioural responses remains poorly understood. Specifically, data characterizing the effect of graded hypoxia on respiratory behaviour, locomotion and breathing pattern have not been described for many invertebrate taxa. These data are important as they aid our understanding of fundamental network mechanisms in metazoan respiratory control. Furthermore, while O2 chemoreceptors have been shown to be critical for rCPG modulation and adaptation to hypoxia, the mechanisms of hypoxic signal transduction and O2-sensing, as well as the functional relationship between multiple peripheral and central chemoreceptors remains uncertain. This thesis has sought to fill these gaps in our knowledge using the Lymnaea stagnalis model system wherein the neural correlates of aerial respiratory behaviour have been previously defined. Here, I demonstrate how graded environmental hypoxia produces adaptive changes in Lymnaea aerial respiratory behaviour by altering respiratory parameters, breathing pattern and plasticity. Moreover, I have identified a distributed peripheral O2 chemoreceptive network, which provides significant modulation of rCPG activity. Finally, I have defined the ability of central hypoxia to modulate rCPG activity and connectivity. Taken together, these studies fill significant gaps in fundamental knowledge vis-à-vis the mechanisms by which highly plastic respiratory neural networks collect and integrate information about the O2 environment in order to produce adaptive respiratory behaviour.
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    Pre- and postsynaptic regulation of synapse formation and synaptic plasticity
    (2002) Munno, David William; Syed, Naweed I.
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    Presynaptic modulation of a central cholinergic synapse by serotonin
    (2007) McCamphill, Patrick; Syed, Naweed I.
    Neuromodulation is central to all nervous system function, although the precise mechanisms by which neurotransmitters affect synaptic efficacy between central neurons remains to be fully elucidated. In this study, I examined the neuromodulatory action of serotonin (5-Hydroxytryptamine or 5-HT) at central synapses between identified neurons from the pond snail Lymnaea stagnalis. Using whole-cell voltage clamp and sharp electrode recording, I show that 5-HT strongly depresses synaptic strength between cultured, cholinergic neuron visceral dorsal 4 (VD4- Presynaptic) and its serotonergic partner left pedal dorsal 1 (LPeD 1 - postsynaptic ). This inhibition was accompanied by a decrease in synaptic depression, but had no effect on postsynaptic input resistance, indicating that it is of presynaptic origin. In addition, serotonin inhibited the presynaptic calcium current (lea) on a similar time course as the change in synaptic transmission. Inclusion of the non-hydrolysable GDP analoge, GDP-??-S, in the presynaptic pipette inhibited the serotonin mediated Ca2+ current depression, as did the membrane impermeable inactive cAMP analoge 80H-cAMP. A model depicting a negative feedback mechanism is presented, where serotonin either present in the extracellular milieu, or released from the postsynaptic cell may act back on the presynaptic cell to inhibit its voltage gated calcium channels through a G-protein coupled, cAMP-mediated second messenger system.
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    Role of electrical activity in trophic factor-mediated synapse formation
    (2002) Hennessy, Deirdre Ann; Syed, Naweed I.
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