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Several endogenous amino acids including L-glutamate and L-aspartate have potent excitatory effects in the central nervous system. They are thought to act as synaptic transmitters in many neural pathways including those in the spinal cord. Three distinct receptors have been described through which these excitatory amino acids exert their effects. These are referred to as quisqualate, kainate and N-methyl-D-aspartate (NMDA) receptors, after the exogenous excitants most specific for each. In addition, sub-types of the NMDA receptor have been proposed to account for differences observed in the actions of the endogenous excitant quinolinate (2,3-pyridine dicarboxylate) in various regions of the nervous system. The characterization of excitant amino acid receptors has been accomplished primarily using two or more potent antagonists which include D-(-)-2-amino-5-phosphonovalerate (APV), a specific NMDA antagonist, and kynurenate, a compound related to quinolinate which potently attenuates the actions of NMDA- and kainate-like excitants. Structure-activity studies of amino acid receptors were undertaken using standard extracellular recording and iontophoretic techniques in the dorsal horn of the spinal cord in vivo, and compared with the neocortex of the rat. In addition, a spinal cord slice preparation was developed wherein dorso-ventral longitudinal slices were prepared from the lumbar enlargement of weanling rats (50 - 125 g). The slices were maintained in an "interface" tissue bath of novel design. Extracellular recording of several hours duration and up to 8 hours after slice preparation were routinely possible. Conformationally restricted analogues of glutamate, aspartate and quinolinate were examined for agonist and antagonist actions in the rat spinal cord in vivo and in vitro. Compounds found to be excitants were compared directly with quisqualate, kainate, and NMDA for sensitivity to blockade by APV and kynurenate applied both iontophoretically and in the bathing medium; antagonist dose-response curves were constructed for the actions of APV and kynurenate against quisqualate, kainate, quinolinate and NMDA. The conformationally restricted compounds found to be antagonists were examined to determine their potency and specificity against excitations elicited by quisqualate, kainate, quinolinate and NMDA. Although quinolinate is known to be NMDA-like in the hippocampus and cortex, when compared to quisqualate, kainate and NMDA in the spinal cord in vitro, it proved to be unique. A fourth receptor (the "QUIN" receptor) is proposed to account for its actions in the spinal cord. Three of the isomers of 1-amino-1,3-cyclopentane dicarboxylate (ACPD), conformationally restricted analogues of glutamate, were potently blocked by APV and KYNA and were therefore classified as NMDA-like. The fourth, D-trans-ACPD. was indistinguishable from quinolinate in terms of both potency and sensitivity to antagonists. The (-) isomer of trans-1-amino-1,2-cyclopentane dicarboxylate proved to be an antagonist with greater potency against excitations elicited by quisqualate and kainate than those of NMDA. These findings are, in many ways, different from what has been observed in the hippocampal slice. Several pyridine derivatives were examined; 2,5- and 2,6-pyridine dicarboxylate were weak excitants behaving like quisqualate in the presence of APV and kynurenate. No other pyridines were excitatory; however 2,4-pyridine dicarboxylate was observed to be a weak, non-specific antagonist similar in action to acridinate (an antagonist closely related to kynurenate). None of the pyridine derivatives, save quinolinate, are excitatory in the hippocampus. Structural analysis of the active compounds tested, in consideration of previous studies, shows that three points of attachment (two carboxyl and one amino group) are necessary for activation of NMDA, quisqualate and quinolinate receptors in the spinal cord. The location of the distal or y-carboxyl group relative to the a ionic groups appears to be the primary factor determining the activity of a conforrnationally restricted compound. The absolute distance between the Y-carboxyl and α-carbon appears to play a secondary role in determining the action of a compound. / Medicine, Faculty of / Graduate

No description available.

New neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the forebrain after eliminating bulb neurons. We found the life-span of newborn neurons in the absence of synaptic targets was shortened, but the timing of maturation was not delayed. In addition, SVZ cells continued to divide and migrate to the damaged bulb, and the migration of newborn cells in the RMS on the contralateral side was delayed at 2 weeks post-BrdU. Also, the proliferation of cells in dentate gyrus of the hippocampus was not affected by OB damage at 3 weeks post-lesion, though lesion affects occurred in the adult SVZ/RMS. / by Huan Liu. / Thesis (M.S.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

Serotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and prefrontal cortex (PFC), in particular, are sensitive to changes in ambient temperature (Tamb). The toxic increase of 5-HT is postulated to occur due to the temperature-dependent activation of these receptors that promotes a positive feedback mechanism. Our results suggest that changes in Tamb can either exacerbate or alleviate the symptom and that this is mediated by the 5-HT2A receptors. Understanding the mechanism involved in elevating Tcor is imperative in treating and preventing the disorder. / by Swapna Krishnamoorthy. / Vita. / Thesis (M.S.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

The rodent hippocampus is critical for processing spatial memory but its contribution to non-spatial, specifically object memory is debated. The cognitive map theory of hippocampal function states that the hippocampus stores relationships of goal locations (places) to discrete items (objects) encountered within environments. Dorsal CA1 place cells were recorded in male C57BL/6J mice performing three variations of the novel object recognition paradigm to define "object-in-context" representation of hippocampal neuronal activity that may support object memory. Results indicate, (i) that place field stability is higher when polarizing environmental cues are provided during object recognition; (ii) hippocampal place fields remain stable throughout the novel object recognition testing without a polarizing cue; and (iii) time dependent effects on stability when objects were dissociated from the context. These data indirectly support that the rodent hippocampus processes object memory, and challenge the view that "object-in-context" representations are formed when mice perform novel object recognition task. / by Herborg Nanna âAsgeirsdâottir. / Thesis (M.A.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

SK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal-dependent object memory, contextual and cued conditioning, and trace fear conditioning was examined. The results demonstrated that pre- but not post-training systemic administration of GW542573X impaired object memory and trace fear memory in mice 24 h after training. Contextual and cued fear memory were not disrupted. These current data suggest that activation of SK1 subtype-containing SK channels impairs long-term memory. These results are consistent with converging evidence that SK channel activation suppressed behaviorally triggered synaptic plasticity necessary for encoding hippocampal-dependent memory. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Thesis (Ph. D.)--University of Montana, 2007. / Title from title screen Description based on contents viewed Oct. 12, 2007. Includes bibliographical references (p. 151-177).