Date of Award


Degree Type


Degree Name

Master of Science




Dr. John MacDonald


Synaptic plasticity of glutamatergic transmission is thought to be the cellular basis for learning and memory. However, the precise mechanisms that regulate the induction of plasticity are not currently understood. In the CA1 region of the hippocampus, the peptide hormone, PACAP (pituitary adenylate cyclase activating polypeptide) acting through the PAC1 receptor (PAC1R) initiates a cascade intracellularly which regulates N- methyl D-aspartate receptor (NMDAR) function, facilitating long term potentiation (LTP). We predicted that endogenous PACAP is active following high frequency stimulation during extracellular recordings from rat and mouse hippocampal slices and will lower the threshold for induction of LTP. Data from PACAP knock-out mice support this hypothesis; however pharmacological manipulation of LTP by PACAP was variable. Our data suggest the PAC1R couples to two pathways with opposing effects on NMDAR function; the NMDAR attenuating arm can be blocked by a phosphatase inhibitor resulting in a more robust enhancement of NMDAR function by PACAP.



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