Investigating Psychiatric Symptoms of Dementia
2024 Award: $110,000
Psychiatric symptoms like agitation, aggression, disinhibition, and impulsivity, amongst others, are common psychiatric symptoms that may precede cognitive decline that is associated with dementia. This project uses a mouse model of dementia (the P301S tauopathy model) to mechanistically examine these psychiatric symptoms antecedent to cognitive decline. We hypothesize that we will observe differences in neurotransmission (both dopaminergic and glutamatergic) in these animals as compared to age matched controls. Furthermore, we expect to observe differences in responses to commonly prescribed psychiatric medications in these mice. By uncovering neural mechanisms impinged upon by tauopathy, we hope to aid in the discovery of biomarkers and development of therapies to alleviate the symptoms associated with dementia.
Need/Problem: Behavioral and psychiatric symptoms of dementia (including but not limited to hyperactivity, agitation, mood disturbance, aggression) often precede cognitive decline, but the neural mechanisms that drive these neuropsychiatric symptoms are not well understood. If we understand how critical brain regions are impacted by these disorders, we can develop mechanisms for interventions at earlier time points.
Grant Summary: Behavioral and psychiatric symptoms of dementia (including but not limited to hyperactivity, agitation, mood disturbance, aggression) often precede cognitive decline, but the neural mechanisms that drive these neuropsychiatric symptoms are not well understood. If we understand how critical brain regions are impacted by these disorders, we can develop mechanisms for interventions at earlier time points.
Goals and Projected Outcomes: I anticipate that this funding will result in at least 2 manuscripts. One for aim 1 where we examine dopamine dynamics at critical periods in development of the pathology. The second paper will focus on the BLA to striatal circuit and will probe plasticity across development. If we can mechanistically understand how tauopathy changes this critical circuitry, we will be well poised to think about strategies for early intervention to prevent some of the psychiatric symptoms associated with dementia. These data will also allow us to submit a grant to NIH to receive additional funding in these domains.
Zoe McElligott, PhD
Grant Details: We will use techniques that are well established in the lab to examine this circuitry: fast-scan cyclic voltammetry (FSCV) and whole-cell slice electrophysiology (ephys). We will also employ optogenetic strategies for circuit specific targeting. These techniques will allow us to examine how “plastic” these circuits are across development in the tauopathy model. Additionally, it will provide insight into how these circuits may change during the course of regular aging, something that is not well understood or appreciated.
