Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thèse (M.Sc.)--Université Laval, 2007. / Bibliogr.: f. [59-66]. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.

High frequency repetitive stimulation of an excitatory input in the hippocampus results in a post-tetanic potentiation (PTP) of short duration (about 3 min) that can be followed by a long-term synaptic potentiation (LTP) of the same excitatory input (Schwartzkroin and Wester, 1975; Andersen et al., 1977). It has been reported that this tetanus-induced LTP cannot be elicited in a Ca²⁺-free medium and is therefore a Ca²⁺-dependent process (Dunwiddie et al., 1978; Dunwiddie and Lynch, 1979; Wigstrӧm et al., 1979). Whether the induction of LTP is directly dependent upon Ca²⁺, or whether, Ca²⁺ is required because synaptic transmission is needed to initiate certain postsynaptic process(es) (a postsynaptic depolarization, for instance) leading to LTP, is unknown. Recent studies from this laboratory showed that both short-term potentiation (STP; with a duration resembling PTP) and LTP can be associatively induced if activation of a test input co-occured with either a tetanic stimulation of separate excitatory inputs or a sufficient depolarization of the postsynaptic neurone (Sastry et al., 1985). In this study, experiments were performed to investigate (1) whether associative STP could be induced when activation of the test input preceded or followed the onset of the conditioning train and (2) whether LTP could be induced in the absence of Ca²⁺ in the extracellular medium if sufficient depolarizations of the presynaptic terminals and postsynaptic neurones were provided. All experiments were performed using the transversely sectioned hippocampal slice preparation. Test stimuli were delivered via an electrode located in the stratum radiatum while the conditioning tetani (100 Hz, 10 pulses per train) were delivered via another electrode located in the recorded from the apical dendritic area of CA₁ neurones. After the initial control stimulation period, 5 conditioning tetani were given at a frequency of 0.2 Hz. The test stimuli either preceded (-) or followed ( + ) the onset of each conditioning train by 0 to 100 ms. When the test stimulus followed the onset of each conditioning train, there was significant STP of the test EPSP up to a conditioning-test interval of +80 ms. When the test stimulus preceded the onset of each conditioning train, there was significant STP of the test EPSP up to a conditioning-test interval of -50 ms. Conditioning tetani that were given without co-activation of the test input resulted in a subsequent depression of the test EPSP. It is suggested that either the test or the conditioning input can initiate some postsynaptic process(es) which can in turn affect the activated presynaptic terminals to increase transmitter release or alter the subsynaptic dendritic properties. For studying the possibility of the induction of LTP in the absence of Ca²⁺ in the extracellular medium, population EPSPs were recorded from apical dendritic area of CA₁ neurones in response to stratum radiatum stimulation. After the control stimulation period, slices were exposed either to Ca²⁺-containing or Ca²⁺-free (with Mn²⁺ and Mg²⁺ replacing Ca²⁺) medium, with the concentration of KC1 at 10 to 80 mM. Long-term potentiation of the population EPSPs was observed following the exposure to high K⁺ in Ca²⁺-free media. Following a brief period of potentiation initially, population EPSPs often exhibited a tendency toward depression after exposure to high K⁺ in Ca²⁺-containing media. LTP induced by high K⁺ in Ca²⁺-free medium could also be observed when a fixed number of axons were being activated, indicating that a recruitment of presynaptic fibres cannot entirely account for the potentiation. LTP of the depolarizing commands were paired with activation of the stratum radiatum while the slices were exposed to Ca²⁺ -free medium (normal concentration of KC1). These results suggest that extracellular Ca²⁺, synaptic transmission and thus subsynaptic receptor activation are not necessary for the induction of LTP as long as sufficient depolarizations of the presynaptic terminals and postsynaptic neurones are provided. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 91-102).

The 'local circuits' of the mammalian neocortex are defined within cortical columns less than 1mm across. There is mounting evidence that these fine-scale neural networks are an important organisational and functional unit. However, detailed study of the local circuitry is hampered by considerable technical difficulties; computer-based modelling therefore offers an important approach to understanding their basic properties. In this thesis, computer simulations are used to examine some of the fundamental questions associated with this class of neural network. We describe a spiking-network model which is inspired by anatomical and physiological study of local neocortical circuitry. Small, heterogeneous circuits are constructed from regular firing, rhythmic bursting and fast spiking neurons. These cells interact strongly through dynamic connections; synapses exhibit facilitation, depression, or a hybrid form of non-associative plasticity. A fast, asymmetric Hebbian process is also examined as a model of the 'Malsburg synapse', and is implemented in parallel with the non-associative fonns of plasticity. Exploration proceeds in three stages using a bottom-up methodology. First, we investigate the dynamical repertoire of the individual classes of circuit; the significance of architectural variation between circuits is addressed, and we examine the influence of fast adaptive processes in shaping network dynamics. Guided by available experimental data, circuits are connected in the second stage to create larger architectures; these are used to study interactions between the circuits. In the third stage, the inhibitory circuits implement surround and feedback inhibition, and local circuit effects of these two contrasting models are explored. Simulation results offer novel links between disparate experimental data. They also indicate how variation in the architecture of particular local circuits, and the different classes of connection between these circuits, might have functional pertinence. More generally, our findings suggest how this style of network may support a highly flexible, dynamically configurable computational architecture.

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Thesis (Ph. D.)--University of Oregon, 2006. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 104-113). Also available for download via the World Wide Web; free to University of Oregon users.

Recent evidence has challenged the prevalent view that neural factors induce the formation of a de novo postsynaptic apparatus during development of the vertebrate neuromuscular junction. The latest experiments suggest an alternative, muscle-dependent model in which the muscle induces the nascent postsynaptic apparatus and sets the location of the future synapse. Once contacted by the incoming axons, these sites, laid out in a pre-pattern in the central area of developing muscle fibers, mature into synapses by the combined action of neural factors such as agrin and ACh. In this study, I sought to provide a test in mammals for these two models of neuromuscular synaptogenesis. Previously, our laboratory showed that continuous muscle expression of constitutively active ErbB2 (CAErbB2) during embryogenesis leads to synaptic loss, exuberant axonal sprouting and lethality at birth. Here, I transiently induced CAErbB2 during midgestation and examined the process of synapse restoration after inducer withdrawal. Centrallyenriched AChR transcription and AChR clustering were abolished as a result of transient CAErbB2 induction. After inducer withdrawal, synapses were restored but were distributed widely over the entire surface of the diaphragm. Under the nerve-dependent model, this distribution would have been explained by the wide pattern of axonal sprouting triggered by CAErbB2 expression. Yet, in the absence of the nerve, introduced in our transgenic animals by mating to Hb9+/- mice, a very similar, wide distribution of aneural AChR clusters was generated. Thus, even in a case where the central pre-pattern of AChR transcription and clustering is missing, it is the muscle, and not the nerve, that seems to set the site for synapse formation. My results support a muscle-dependent model for the induction of neuromuscular synaptogenesis in mammals.