Dr. Don Davies, York University – candidate for the Black/Indigenous faculty position in Biomedical Sciences will be giving a Research Talk on Thursday June 1st at 12:30p in Room 3708 ECLA.
Probing the nature of changes in memory and synaptic transmission in rodent models of Alzheimer’s disease
Abstract: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder, characterized by cognitive impairments, including memory loss. Brain cells communicate through connections, known as synapses, that contain specialized receptors. One type of receptor, NMDA receptors, determines our ability to learn and remember. NMDA receptors have been linked to AD and working memory, suggesting that understanding how they are altered in AD will reveal the nature of this brain disorder. Therefore, we tested the effects of an NMDA receptor antagonist on a working memory capacity task. The dorsomedial striatum (dmSTR) and medial prefrontal cortex (mPFC) are two brain structures affected in AD. Blockade of NMDA receptors in dmSTR but not mPFC reduced working memory capacity in rats.
Variants in Apolipoprotein E (APOE) are predictive of resilience to or predilection for AD. There are 3 APOE gene polymorphic alleles (E2, E3, E4). Interestingly, E2 may be neuroprotective whereas the E4 allele is found in ~40% of those with AD. Consistent with humans, mice expressing E4 (APOE4-Knock-in; KI) demonstrate hallmarks of AD including memory impairment and altered synaptic plasticity. However, a combination of conflicting results and a paucity of data examining alternative mechanisms raises the question: What is the nature of synaptic plasticity changes in mice harboring E4?
To address this, we used a cellular analog of memory known as long-term potentiation (LTP), focusing on how quickly it decays as a proxy for accelerated memory loss. Surprisingly, LTP decayed faster in APOE3-KI mice when compared to APOE4- or APOE2-KI mice, which may be due to the young adult age of the mice. Future experiments will examine various forms of synaptic plasticity and working memory in APOE-KI mice at various ages.