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Differential involvement of glutamate receptors in neuronal responses of the cerebral cortex

I studied how glutamate receptor-mediated responses, spatial arrangements, intrinsic properties and molecular specificity of cells serve cortical functions. I tested whether two somatosensory submodalities in the primary somatosensory (SI) cortex can be distinguished by glutamate receptor involvement in vivo. Low-threshold responses evoked by innocuous stimuli had a short-duration and long-duration component. The short-duration responses were mostly mediated by AMPA/kainate receptors and the long-duration responses involved the additional recruitment of NMDA receptors. High-threshold responses evoked by noxious stimuli were unimodal and mediated by both AMPA/kainate and NMDA receptors throughout the entire response. During noxious stimulus trials, an increase in baseline activity in SI cortical cells was observed. I attribute the changes in baseline activity to cells in the medial thalamic nuclei, which project to the SI cortex and are involved in the affective-motivational aspects of nociceptive signalling. To gain insight into the influence of synaptic organisation of a well-defined cortical area, I studied in vitro whether the intrinsic properties of two anatomically well-defined nonpyramidal cells in the hippocampus can provide clues into the modulation of neuronal signalling. During a depolarising current pulse, O-LM and O-Bi cells were distinguished by their accommodation of action potentials depending on the early or late part of the response. Also, during a hyperpolarising current pulse, O-LM cells displayed a prominent voltage 'sag' as compared to O-Bi cells. Both cell types contain somatostatin and I showed that O-LM cells express the metabotropic glutamate receptor type 1α. Although O-LM and O-Bi cells have a similar somatodendritic position their different axonal arbours imply that they are involved in the feedback modulation of the entorhinal and CA3 glutamatergic influences, respectively. I also found that contrary to previous reports not only somatostatin but also vasoactive intestinal polypeptide containing cells express mGluR1α, which might facilitate their oscillatory responses. To relate the action potential discharge of specific cortical cell classes to behaviourally relevant network activity, I also sought to identify hippocampal cells following in vivo recording. Novel information was provided for both the temporal and anatomical properties of cells not recorded previously. In particular, a putative interneuron targeting nonpyramidal cell and backprojection cell was recorded in relation to theta field events. A novel nonpyramidal projection cell was recorded in relation to sharp wave field events. A remarkable specificity was found in the dendritic and axonal patterns of these cells. The results show that distinct types of glutamate receptors are differentially involved in cortical function. The intrinsic properties and expression of mGluR1α in particular is highly specific in distinct nonpyramidal cell classes.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:365721
Date January 2001
CreatorsPollard, Marie
ContributorsSomogyi, Peter
PublisherUniversity of Oxford
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://ora.ox.ac.uk/objects/uuid:f6c716f7-021d-4d73-8108-493fdd51e8ae

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