Microiontophoresis as a technique to investigate Spike Timing Dependent Plasticity

Spike timing dependent plasticity (STDP) is a form of synaptic plasticity that depends on the relative time of activation of a presynaptic neuron and its postsynaptic neuron. STDP in the synapses made by Schaffer collateral afferents onto hippocampal CA1 pyramidal neurons (CA3-CA1 synapses) is NMDA receptor dependent. The objective of the current study was to develop and test a technique of glutamate iontophoresis that could replace the role of presynaptic neurotransmitter release at the CA3-CA1 synapse, so that the postsynaptic mechanisms involved in the induction of STDP could be isolated for study. Therefore, this document describes: (1) fabrication of electrodes that could be used for millisecond-level microiontophoresis in acute slice preparations of the juvenile rat hippocampus; (2) characterization of the properties and limitations of microiontophoresis in slice tissue, specifically for activation of postsynaptic ionotropic glutamate receptors at the CA3-CA1 synapse; (3) induction of STDP by pairing microiontophoresis with postsynaptic depolarization; (4) characterization of the properties and limitations of microiontophoretically induced STDP. It was determined that microiontophoresis is a viable technique to study the postsynaptic mechanisms of STDP at the CA3-CA1 synapse. My results also show that microiontophoretically induced STDP exhibits many of the same general properties as STDP induced either synaptically or by exogenously applied agonists. Microiontophoretically induced STDP also exhibits other features that will need to be considered during the design and interpretation of further experiments