Abstract

The present thesis examined whether acetylcholine (ACh) and 17-β estradiol (E2) modulate object-recognition memory (ORM) and perirhinal cortex (PRh) function. ORM was assessed using the Novel-Object Preference (NOP) test or the delayed non-match-to-sample (DNMS) task. The first goal was to investigate whether acetylcholine (ACh) acts via muscarinic receptors (mAChR) in the PRh to modulate novelty preference and novelty-related neuronal activation. Male rats received intra-PRh infusions of a mAChR antagonist or vehicle in the PRh before or after the familiarization phase of the NOP test, then tested 4- or 24-hr later. These infusions were also given before novel- or familiar-object exploration. The antagonist prevented novelty preference regardless of retention delay and timing of infusion. While novel-object exploration resulted in increased PRh activation, this increase was prevented by mAChR antagonism. These results are consistent with the idea that ACh (via mAChR in the PRh) modulates novelty preference and neuronal activation following novel-object exploration.
A second goal was to determine whether intra-PRh modulates ORM and PRh-mediated synaptic plasticity in ovariectomized rats. Intra-PRh infusions of E2 or vehicle were given immediately before, immediately after, or two hours following the familiarization phase of the NOP test. Intra-PRh infusions of E2 or vehicle were also given before the DNMS task. Enhanced novelty preference was observed on a 72-hr retention test when E2 was administered immediately before or after familiarization. Intra-PRh E2 reduced accuracy scores on the DNMS task following a 3-min retention delay. A subsequent study examined whether E2 modulates ORM via estrogen receptor beta (ERβ). Intra-PRh infusions of a selective ERβ agonist enhanced novelty preference following a 4- and 72-hr retention delay, but had no effect on accuracy on the DNMS task. The final study compared synaptic density of PRh neurons following proestrous and estrous, and following high E2 replacement or no replacement in ovariectomized rats. High levels of E2 were associated with reduced synaptic density. These results support the idea that while E2 (via ERβ) enhances novelty preference, it impairs ORM (independent of ERβ). The modulatory effect of E2 on synaptic density in the PRh is a potential mechanism through which E2 influences ORM.