Barry, Michael Francis; (1997) An investigation into the induction of non-associative long-term synaptic depression in the ca1 region of the rat hippocampus in vitro. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Non-associative long-term depression (LTD) is a long-term reduction in the strength of synaptic transmission that occurs at inactive synapses following a period of postsynaptic depolarization. I have investigated the importance of intracellular Ca2+ levels in the induction of non-associative LTD in single pyramidal cells in the CA1 region of the rat hippocampus in vitro. Postsynaptic Ca2+ entry on depolarization was manipulated by changing the amount of Ca2+ in the bathing medium ([Ca2+]o). Following unpaired postsynaptic depolarization, a significant non-associative LTD could be induced in about half of the cells tested when slices were bathed in a lower [Ca2+]o) than normal but not when they were bathed in a higher [Ca2+]o. Postsynaptic depolarization in the presence of the GABAA receptor antagonist bicuculline, which also affects intracellular Ca2+ concentration ([Ca2+]i), failed to induce non-associative LTD in the naive slice. However postsynaptic depolarization in bicuculline could produce significant non-associative depotentiation of previously potentiated synapses in about half of the cells tested. To directly measure the rise in [Ca2+]i following postsynaptic depolarization, cells were filled with the calcium indicator Fura-2. Postsynaptic depolarization applied to cells in bathing media designed to lower postsynaptic calcium entry, resulted in a reduction in the rise of dendritic and somatic [Ca2+]i compared to in the normal bathing medium in most cases. In many but not all of these cells LTD was also observed. Although LTD induction occurred with a higher probability when the rise in [Ca2+]i was experimentally reduced, there was no direct correlation found between the amount of synaptic depression and the magnitude of the [Ca2+]i rise in the apical dendrite, or the soma (r2 = 0.18 and 0.02 respectively). Further experimentation is needed to measure the [Ca2+]i in the close vicinity of the test synapses in order to clarify the influence [Ca2+]i has on non-associative LTD induction.

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