Samuel Brunwasser
Program: Neurosciences
Current advisor: Keith B. Hengen, PhD
Undergraduate university: Arizona State University-Tempe
Research summary
The relationship between brainwide functional decline and accumulation of pathological protein aggregates in Alzheimer’s disease (AD) is complex and not well understood. A set of highly interconnected cortical regions known as the Default Mode Network (DMN) exhibits selective vulnerability to both functional decline and amyloid beta (Aβ) plaques in early AD. One possibility is that early Aβ accumulation in the DMN drives vulnerability. However, it is unknown whether there is something intrinsic to neuronal projections within the DMN that biases these circuits towards dysfunction. For my thesis work, I employed chronic, continuous, multisite in vivo electrophysiology in freely behaving mice to obtain single unit recordings from multiple brain regions in a mouse model of Alzheimer’s Disease with global cortical Aβ burden (APP/PS1) in order to directly test this hypothesis. Specifically, I tracked the interactions of a population of neurons within a DMN region and two additional populations that comprise monosynaptic targets, one within and the other outside the DMN. In addition, I recorded from single neurons in CA1 and examined hippocampal sharp-wave ripple triggered interactions between in-DMN and out-DMN cortical circuits. I examined the statistics of local activity as well as inter-regional communication in a region, genotype, and brain-state dependent manner. Our data reveal dysfunction restricted to within-DMN projecting circuits. In contrast, communication along neuronal projections that originate in the DMN but target non-DMN populations are equivalent in APP/PS1 and control mice. Circuit dysfunction is found to be most evident in NREM sleep, on the timescale of hours as well as within sharp-wave ripples, a stereotyped hippocampal event that contributes to memory consolidation in the cortex. Our results indicate that neighboring cells in the DMN exhibit differential intrinsic vulnerability to amyloid injury dependent on their projection targets.
Graduate publications