Date of Award

Spring 1-1-2013

Document Type


Degree Name

Doctor of Philosophy (PhD)


Psychology & Neuroscience

First Advisor

Susan L. Patterson

Second Advisor

Steve F. Maier

Third Advisor

Jerry W. Rudy

Fourth Advisor

Robert L. Spencer

Fifth Advisor

Gregory Carey


It is well accepted that early stages of cognitive decline and memory loss involve altered synaptic plasticity in the hippocampus and related structures. It has been proposed that calcium homeostasis in principal neurons of the hippocampus becomes `dysregulated' with age. Specifically, a decline in N-methyl-D-aspartate receptors (NMDA receptors) and an increase in L-type voltage-dependent calcium channels may reduce overall neuronal excitability and synaptic plasticity. This is believed to shift synaptic plasticity in the aged brain away from long-term potentiation (LTP) and toward long-term depression (LTD). Another major change that occurs with age is increased brain inflammation. It has been demonstrated in aged rodents that a peripheral immune challenge with Escherichia coli triggers a prolonged inflammatory response in the hippocampus, which impairs long-term memory consolidation in the days following. Because this process is dependent upon synaptic plasticity in region CA1 of the hippocampus, we explored LTP and LTD there as well changes in NMDA receptors and L- type calcium channels. We found that a peripheral infection in aged rats decreases LTP following theta-burst stimulation but increases LTD following low frequency stimulations, both of which are dependent upon NMDA receptors. However, infection decreases a more robust LTP following high frequency stimulation in young rats, and reduces the contribution of L-type calcium channels in both young and aged rats. These effects are not associated with major changes in NMDA receptors or L-type calcium channels in the synapse, and only the GluN2B subunit of NMDA receptor is significantly increased. Inflammation has been demonstrated to increase neural excitability, yet the overall effect of inflammation in our studies was reduced LTP and enhanced LTD. It is therefore possible that some of the changes in calcium homeostasis and synaptic plasticity that occur with age are either caused by or activated as a neuroprotective mechanism against increased inflammation.