Parietal-hippocampal network in the triple transgenic mouse model of Alzheimers

Florida State University, Tallahassee FL

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Abstract

Alzheimer?s disease is devastating for both individuals and society. Getting lost and memory impairments are major symptoms of the disease. Similarly, rodent models of Alzheimer?s disease also ?get lost? (e.g., impaired spatial navigation). Emerging evidence suggests abnormal communication between the posterior parietal cortex (PPC) and hippocampus in humans with Alzheimer?s. The objective of the proposed research is to explore the functionality of the hippocampal-PPC network in an animal model of amyloidosis, in order to assess potential contributions of altered cortico-hippocampal function to Alzheimer?s disease. To do this, I will focus on the triple transgenic mouse model of Alzheimer?s where three major genes associated with familial Alzheimer?s disease are expressed. This mouse model mimics both plaque and tangle pathological hallmarks of the disease with a distribution pattern similar to human patients, including synaptic changes in the limbic system. Specifically, in three different experiments I will: a) continue to assess hippocampal population activity as a potential cause of impairments in triple transgenic mice in using an external (room based) reference frame when their internal position reference frame is disrupted; b) continue to assess both rest related memory replay and functional synaptic connectivity within and across the hippocampus and PPC in the triple transgenic mouse; c) utilize a novel pharmacogenetic approach to test the theory that temporary and specific hippocampal inactivation will produce impairments in memory replay that mimic those seen in animal models. Finally, findings in the triple transgenic model will be confirmed in a newer model of Alzheimer?s that is more similar to sporadic Alzheimer?s in humans.