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Developmental expression of N-methyl-D-aspartate and gamma-aminobutyric acid receptors in the rat basal gangliaLau, Wai Kit Jaeger 01 January 2004 (has links)
No description available.
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An investigation of the role of hippocampal NMDA receptors in spatial learning /Tirado Santiago, Giovanni. January 2006 (has links)
No description available.
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Characterization of D-Aspartate Receptor Currents in Aplysia californicaCarlson, Stephen Lee 06 October 2010 (has links)
D-Aspartate (D-Asp) is an endogenous compound found in the central nervous system (CNS) of a variety of organisms. Despite its prevalence, however, relatively little understood of its physiological role. The prevailing theory is that D-Asp is an alternate agonist of N-methyl-D-aspartate receptor (NMDAR) channels. The goal of this work was to characterize the currents activated by D-Asp in neurons Aplysia californica, focusing on cells of the buccal S cluster (BSC). First, a general electrophysiological characterization was carried out, examining ion permeability, agonist dose-response, and the kinetics of activation, inactivation, and desensitization. D-Asp activated non-specific cation currents characterized by permeability to Na+ and K+. D-Asp-induced currents shared similar current-voltage relationships and time courses of activation and inactivation with L-glutamate (L-Glu)-induced currents. D-Asp currents, however, were subject to prolonged desensitization. Additionally, D-Asp activated currents independently of L-Glu, the known agonist of NMDAR channels, suggesting a non-NMDAR-dependent role of D-Asp. Next, select antagonists were used in an effort to pharmacologically characterize D-Asp receptor channels. These experiments suggested that D-Asp whole cell currents may be characterized by activation of multiple receptor sites, including NMDARS, excitatory amino acid transporters (EAATs), and a putative non-L-Glu D-Asp receptor. Furthermore, bath-applied D-Asp attenuated L-Glu-activated currents. Finally, D-Asp currents were compared to those evoked by acetylcholine (ACh) and serotonin (5-HT) in BSC cells. Results suggested that D-Asp activated receptor channels independently of ACh and 5-HT. Ten minute bath application of 5-HT was found to potentiate D-Asp current responses, likely through activation of a protein kinase C (PKC)-dependent mechanism, suggesting that D-Asp induced currents may be subject to synaptic plasticity associated with learning. While the identity of the putative D-Asp receptor remains elusive, the current work has advanced our understanding of the role D-Asp may play in the nervous system. These results should provide the groundwork for future studies aimed at identifying this unknown receptor channel, as well as investigation of the potential relationship of D-Asp receptor modulation to learning and memory in Aplysia, which may have relevance in higher organisms.
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Multiscale docking using evolutionary optimisationHuggins, David John January 2005 (has links)
Molecular docking algorithms are computational methods that predict the binding site and docking pose of specified ligands with a protein target. They have proliferated in recent years, due to the explosion of structural data in biology. Oxdock is an algorithm that uses various techniques to simplify this complex task, the most significant being the use of a multiscale approach to analyse the problem using a simple representation in the early stages. Oxdock is shown to be a very useful tool in computational biology, as exemplified by two cases. The first case is the analysis of the NMDA subclass of neuronal glutamate receptors and the subsequent elucidation of their function. The second is the investigation of the newly discovered plant glutamate receptors and the clarification of their natural ligands. The results in both instances open new areas of research into exciting areas of biology. Despite its effectiveness in solving many problems, Oxdock does fail in a number of circumstances. It is thus important to devise a new and improved method for molecular docking. This is achieved by combining the speed of the multiscale approach with the optimising ability of Evolutionary Programming. This yields an algorithm that is shown to be precise, accurate and specific. The new algorithm, Eve, is then modified to illustrate its potential in both lead optimisation and de novo drug design. These capacities, combined with its ability to predict the location of binding sites and the docking pose of a ligand, highlight the promise of computational methods in solving problems in many areas of biological chemistry.
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Localization of N-methyl-D-aspartate receptor subunit 2 mRNAs within the central nervous system of the weakly electric fish Apteronotus leptorhynchusFinn, Richard James. January 1999 (has links)
Partial cDNAs for each of the four known N-methyl-D-aspartate (NMDA) receptor 2 (NMDAR2A-D) subunits have been cloned from the brain of A. leptorhynchus and are found to display a high degree of sequence homology (83--78% amino acid identity) to their mammalian homologues. In situ hybridization experiments reveal that each transcript has a distinct expression pattern in the apteronotid central nervous system (CNS) and is present in a "mosaic" distribution within important cell types of the electrosensory lateral line lobe (ELL). Apt. NMDAR2A transcript is expressed in forebrain regions as well as throughout the pyramidal cell layer (PCL) and granule cell layer (GCL) of the ELL. Apt. NMDAR2B mRNA is enriched in mid- and forebrain structures as well as the PCL and GCL of the ELL. Apt. NMDAR2C transcript is largely restricted to cerebellar regions but is also found in the PCL and GCL of the ELL's medial, centromedial, and centrolateral segments. Apt. NMDAR2D mRNA is expressed in sites of cell proliferation and in a segmental gradient within granule cells of the ELL.
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NMDA receptor activity is necessary for long-term memory in the non-spatial, hippocampal-dependent, social transmission of food preference taskRoberts, Michael J., 1973- January 2000 (has links)
Memory of some forms requires the hippocampus, a brain structure in the medial temporal lobe that reveals remarkable synaptic plasticity. Most synapses in the hippocampus require NMDA-receptors for the induction of this plasticity. Memories that require the hippocampus may also require NMDA-receptor mediated plasticity. This thesis tested the involvement of NMDA receptor activity in memory for a non-spatial, social learning task that requires the hippocampus: the social transmission of food preference, NMDA receptor antagonist (CPP) injected systemically 55 minutes prior to training impaired performance 72 hours later, but not 48 hours, 24 hours, or 15 minutes later. NMDA receptor antagonist (AP-5) injected into the dorsal hippocampus 30 minutes prior to training also impaired performance at the 72-hour delay. Injections of CPP at 10 minutes or 24 hours post-training had no effect on performance. These results suggest that hippocampal NMDA receptor activity is necessary for stable learning of the non-spatial social transmission of food preference.
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NMDA receptor blockade and spatial learning : a reinvestigationWhite, Lynn H. January 1993 (has links)
N-methyl-D-aspartate (NMDA) receptor activation is believed necessary for certain types of learning. The present experiments investigated the effects of the NMDA antagonist, MK-801, on spatial learning and memory in rats. Experiment 1 tested the effects of MK-801 on the acquisition and retention of a water maze task. MK-801 produced a performance, but not a spatial learning deficit. Experiment 2 tested the effects of MK-801 on the acquisition and retention of a radial arm maze task (RAM). MK-801 had no effect on initial acquisition and retention, but impaired subsequent reversal learning when the pattern of rewarded and unrewarded arms was reversed. Experiment 3 investigated the effects of MK-801 on RAM reversal learning in rats previously trained on the initial task in the absence of drugs. MK-801 produced a dose dependent impairment on reversal learning. These results are consistent with one interpretation that MK-801 impairs the ability to suppress interference from previously learned information.
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An investigation of the role of hippocampal NMDA receptors in spatial learning /Tirado Santiago, Giovanni. January 2006 (has links)
Declarative learning entails the internalization of facts and events. This type of learning depends on the integrity of the hippocampal system. In rodents, spatial learning is studied as a model of declarative learning. In this thesis, electrophysiological and behavioral experiments assessed the role of NMDA receptors in synaptic plasticity and rats' spatial learning and memory. Primed burst potentiation (PBP), a form of synaptic strengthening, was studied in freely-behaving rats treated with NMDA receptor antagonists. The impairments caused by the antagonists correlated with those observed in behavioral studies. The results support the idea that NMDA receptors in the hippocampal system mediate the internalization of the contents and organization of new environmental information, and show that the receptors are not relevant for spatial working memory or performance once a representation of the environment is stable. The results also suggest that stable spatial representations resemble multiple relations of events and do not correspond to topographical maps of an environment. As learning proceeds, representations are activated by smaller subsets of environmental cues, which eventually become sufficient for effective navigation. The representations thus are encoded as relationships of stimuli that share similarities or that are unique to a particular event. The organization of novel information is given through NMDA receptor-mediated synaptic plasticity. This plasticity mechanism could resemble a process similar to the synaptic changes observed during PBP.
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Comparison of two methods for measuring erythrocyte aspartate aminotransferase activity in humansIwakiri, Yasuko 06 March 1995 (has links)
We compared a kinetic method (KM) and a colorimetric method (CM) for
measuring erythrocyte aspartate aminotransferase (EAST) activity. Twenty-three
healthy college students including 7 men and 16 women, aged from 22 to 40 years,
participated in this study. Vitamin B-6 status was assessed by EAST activity
coefficient (EAST-AC), the ratio of EAST stimulated activity by adding PLP in vitro
(EAST-SA) to basal activity (EAST-BA). These subjects' EAST indices (EAST-BA,
EAST-SA and EAST-AC) were compared to their plasma PLP concentration and their
dietary intake of vitamin B-6 as determined by the food frequency questionnaire (FFQ)
and 3-day dietary record.
There was a significant correlation (r=0.59, p<0.01) in EAST-BA obtained by
the two methods, while the correlation of EAST-SA values between the two methods
was not significant (r=0.40, p=0.06). EAST-AC obtained with KM was linearly
associated (r=0.57, p<0.01) to EAST-AC obtained with CM, but was 1.26 times higher (p<0.01) than that with CM. Thus, the method used for the determination of the
normal EAST-AC value needs to be noted. None of EAST indices measured were
significantly correlated with plasma PLP concentration.
There was a high correlation for vitamin B-6 intake (r=0.65, p<0.01) and the
ratio of vitamin B-6 to dietary protein (r=0.58, p<0.01) estimated between the FFQ
and the 3-day dietary record. The results suggested the high validity of the FFQ for
determining vitamin B-6 intake. Neither of these dietary methods was, however,
correlated with any EAST activity indices or the plasma PLP concentration. / Graduation date: 1995
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Modulation of long-term potentiation by the glycine site of N-methyl-D-aspartate receptor in rat hippocampal CA1 pyramidal cells /Krasteniakov, Nicholas, January 1900 (has links)
Thesis (Ph. D.)--Carleton University, 2004. / Includes bibliographical references (p. 118-146). Also available in electronic format on the Internet.
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