Information is transferred between neurons in the brain via electrochemical transmission at specialized cell-cell junctions called synapses. These structures are far from being static, but rather are influenced by plasticity mechanisms that alter features of synaptic transmission as means to build routes of information flow in the brain. Hebbian forms of synaptic plasticity – long-term potentiation and long-term depression – have been well studied and are considered to be the cellular basis of learning and memory, although their positive feedback nature is prone to instability. Neurons are also endowed with homeostatic mechanisms of synaptic plasticity that act to stabilize neural network functions by globally tuning synaptic drive. Precisely how neurons orchestrate this adaptive homeostatic response and how it influences Hebbian forms of synaptic plasticity, however, remains only partially understood. Using a combination of whole-cell electrophysiology, two-photon imaging and glutamate uncaging in organotypic hippocampal slices, I have expanded upon the known repertoire of homeostatic mechanisms that increase excitatory synaptic drive when CA1 hippocampal neurons experience a prolonged period of diminished activity. I found that the subunit composition of AMPA and NMDA receptors, the two major glutamate receptor subtypes at excitatory synapses, are altered which, in addition to increasing synaptic strength, are predicted to change the signaling and integrative properties of synaptic transmission. Moreover, I found that the amount of glutamate released from presynaptic terminals during evoked-transmission is enhanced and that this mechanism might, in part, underlie the uniform cell-wide homeostatic increase in synaptic strengths. Lastly, I found that homeostatic strengthening of synaptic transmission reduced the potential for CA1 synapses to exhibit long-term potentiation, and that this was caused by altered presynaptic release dynamics that impeded plasticity induction. Together, this work highlights several mechanistic strategies employed by neurons to increase excitatory synaptic drive during periods of activity deprivation which, in addition to balancing cellular excitability, alters the metaplastic state of synapses.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/35508 |
| Date | January 2016 |
| Creators | Soares, Cary |
| Contributors | Béïque, Jean-Claude |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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