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Thesis (M.Sc.)--York University, 2005. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 72-82). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11836

In the hippocampus, tetanic stimulation of an input results in a long lasting potentiation (LLP) of synaptic transmission involving that input. While high frequency tetanic stimulations are preferred to elicit LLP, low frequency tetanus induces homosynaptic and heterosynaptic depressions. The present investigations were conducted to (1) analyse the characteristics of pulses in orthodromic and antidromic tetanic stimulations and relate them to post-tetanic changes in evoked potentials (2) determine if potentiation and depression co-occur and (3) determine whether an established LLP in one input is subsequently modified by the initiation of LLP in another input (to the same CAlb neurons) or whether LLP can be reversed by homosynaptic and heterosynaptic depressions and lastly (4) determine how interference or enhancements of calcium and potassium fluxes with pharmacological substances related to potentiation and depression. Experiments were conducted on transversely sectioned rat hippocampal slices. Evoked potentials in subfield CAlb were elicited with stimulations of CAlb axons, commissural (Com), or Schaffer collaterals (Sch). Sch terminal excitability was tested with a stimulating electrode placed in the Sch/CAlb synaptic regions. Recordings were made with microelectrodes positioned in the CAlb cell bodies and/or dendritic regions, and in field CA3. It was found that potentiation and depressions co-occur. Presynaptic volleys accompanied all tested tetanic trains. Similarly, antidromic trains discharged CAlb neurons continuously but did not cause LLP. Low frequency tetanic trains caused facilitated synchronous discharges of CAlb neurons during significant portions of these trains. In contrast, few if any syn- chronous discharges followed high frequency tetanus. Yet high frequency tetanus elicited LLP and low frequency tetanus caused homo- and heterosynaptic depressions. An established LLP could be masked but not reversed by homo- and heterosynaptic depressions but this LLP was not interrupted by subsequently induced LLP of a separate input. Iontophoretic L-glutamate on CAlb cell bodies caused depression which was more pronounced if a tetanus was evoked during L-glutamate ejections. The depressions to low frequency tetanus and L-glutamate were counteracted by verapamil. Lastly, barium and 4-aminopyridine potentiations were reversed with washing. Applications of these drugs did not alter Sch terminal excitability. Tetanus induced during the presence of 4-aminopyridine still elicited LLP. It is concluded that homo- and heterosynaptic depressions are partly due to the accumulation of calcium into the CAlb neurons. The magnitude of calcium entry into presynaptic and postsynaptic regions is governed by the tetanic frequencies evoked. The results are consistent with a presynaptic mediated LLP. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

The electrophysiological properties of dentate granule cells and hippocampal pyramidal neurons were examined with extracellular and intracellular recording techniques in the hippocampal slice. Intracellular analysis revealed that there may exist two populations of granule cells distinguishable by the presence or absence of non-linear current-voltage (I-V) membrane properties (anomalous rectification, AR). The granule cells exhibiting AR also maintained greater resting membrane potentials and action potential (AP) amplitude values. The membrane input resistance (Rn) and time constant (Tc) measurements were similar between the populations in response to hyperpolarizing current injection, but granule cells displaying AR had significantly higher Rn and Tc values in response to depolarizing pulses. Both groups also responded to maintained depolarizing current injection with repetitive AP discharges; however, this response accommodated. Upon termination of the depolarizing current injection, an afterhyperpolarization (AHP) resulted, the amplitude of which appeared to depend on the duration of the depolarizing pulse and not on the number of APs generated during the pulse. Stimulation of either the lateral (LPP) or medial (MPP) perforant paths evoked a monosynaptic EPSP followed by a depolarizing afterpotential (DAP) and a long afterhyperpolarization (LHP). In contrast, antidromic stimulation elicited a depolarizing-IPSP (D-IPSP) and a LHP. Both the DAP and D-IPSP were reversed by membrane depolarization, whereas, the LHP was inverted by membrane hyperpolarization. In all cases, however, the EPSP could not be inverted. Afterpotentials were associated with an increase in conductance, but the change accompanying the LHP was less than the DAP and D-IPSP. In addition, by reducing the [Ca]₀ and increasing the [Mg]₀, the DAP was attenuated and the LHP eliminated. Similar results were also obtained with the GABAB agonist, baclofen. Paired pulse stimulation of either the LPP or MPP resulted in the potentiation of the intracellular EPSP at condition-test (C-T) intervals less than 100 ms; however, simultaneous extracellular records from the granule cell layer (GCL) illustrated depression of the EPSP. The discrepancy between the extra- and intracellular recordings was shown to be related to the presence of the DAP. In addition, the MPP evoked test EPSP at C-T intervals greater than 150 ms exhibited inhibition regardless of whether it was recorded inside or outside the granule cell and this EPSP depression was partially due to the granule cell LHP. The LPP evoked test EPSP potentiated at all C-T intervals less than 1s when recorded from the outer molecular layer (OML) but was inhibited at both the GCL and intracellular recording sites. These data confirmed that postsynaptic processes contribute to the short-term alterations observed with paired pulse stimulation. The typical inhibition-potentiation-inhibition sequence of the perforant path (PP) evoked population spike (PS) was noted at C-T intervals of 20, 80 and 400 ms, respectively. The inhibition of the PS at 20 ms was abolished with perfusion of the GABA antagonist, bicuculline. In contrast, the PS inhibition at 400ms was unaffected by this treatment but was slightly attenuated by the gKca antagonist TEA. A number of factors appeared to contribute to the potentiation of the PS: 1) reduction in AP threshold; 2) the presence of the DAP; and 3) extrasynaptic events. In addition to the PS data from normal tissue, hippocampal slices from chronically kindled rats exhibited depression of the PS at all C-T intervals tested. This augmentation of inhibition was dependent on the presence of hippocampal afterdischarges but not on motor seizures. Perfusing the kindled slices with either bicuculline or lowered [Cl]₀ did not markedly reverse the enhanced inhibition at C-T intervals which displayed dramatic facilitation in normal slices. Intracellular recordings of granule cells obtained from kindled slices also exhibited an increase in the Rn and Tc. Both the alterations in inhibition and membrane characteristics appear to be localized to.the granule cells, since these changes were not observed in CA1 pyramidal neurons. These data indicate that short-term and long-term alterations in granule cell neuronal excitability are partially due to changes in the postsynaptic membrane. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

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A literature review of the schizophrenia brain electrophysiology was undertaken with specific emphasis placed on the topographical distribution of evoked potentials (EPs). The outcomes of this review suggests that schizophrenia brain electrophysiology, demonstrate some differences, but with a variability reflective of the symptom heterogeneity. The literature associated with the use of attentional tasks while recording EPs, tended to demonstrate some consistency. The methodological issues associated with the EEG and EP recordings may also account for this variability. An evoked potential technique, which has been demonstrated to be sensitive to the changes in cognitive processes associated with attention, is the Steady State Probe Topography (SSPT) technique. The SSPT is a combination of both the Steady State Visual Evoked Potential (SSVEP) and the Probe-ERP paradigm. This technique allows the SSVEP to be measured continuously, is relatively insensitive to artifact, and can display the topographic distribution of the SSVEP measures during the attentional task. The technique employs the use of a sixty-four channel EEG recording system. This consists of a multichannel electrode helmet; multichannel amplifier/filter, task presentation computer and a computer controlled data acquisition system. Software was also developed to analyse the recorded brain electrical activity to produce the SSVEP magnitude and phase versus time series for each electrode site. The topographic distribution of the SSVEP measures associated with specific events during attentional tasks could also be displayed. At the time of the pilot study, this technique had not been applied previously to the study of schizophrenia and therefore warranted further study. Two separate studies are reported; an investigative pilot study and a chronic group study. The pilot SSVEP and schizophrenia study was designed to examine the changes in the SSVEP and its topography, during the performance of a number of attentional or activation tasks to examine the possibility of hypofrontality. The tasks selected for the study were those previously used for the examination of hypofrontality with metabolic imaging techniques; the Continuous Performance Task (CPT) and the Wisconsin Card Sort (WCS). The SSVEP was elicited by a superimposed 13Hz flicker on the visual field, while subjects performed computerised versions of the neuropsychological tasks. Topographical maps of the SSVEP magnitude distribution were then interpolated and displayed as an animated sequence synchronised with particular events occurring during the tasks. In comparison to the male control group, male schizophrenic patients exhibited differences in the SSVEP topography for all tasks, possibly reflecting the deficits in behavioural indices. Overall, the findings indicated that the technique demonstrated some merit for further examination of frontal SSVEP topography in schizophrenia. In a larger study of twenty chronic schizophrenia patients, the frontal topographical distribution of the SSVEP was examined. The earlier pilot study finding of reduced frontal SSVEP amplitude was replicated. The issue of hypofrontality in schizophrenia was applied as a possible interpretation.

Copies of author's previously published articles inserted. Bibliography: leaves I-LXIV. Assesses the diagnostic and prognostic value of early electroencephalography (EEG) and somatosensory evoked potential studies in cortical and non-cortical ischaemic stroke. Both conventional and topographic/quantitative studies were performed. A parallel study was carried out on healthy volunteers to provide an effective control. Equipment and quantitative EEG (qEEG) variability was also assessed.

Thesis (M.A.)--York University, 1998. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 52-59). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ39233.