Effect of neural synchronization on hippocampal representations in health and under conditions of Aβ-pathology
1 DZNE
Disrupted neural oscillations and memory are common features of Alzheimer's disease (AD). Our previous studies have demonstrated the potential to restore the temporal organization of theta oscillations by utilizing LFP-guided closed-loop optogenetic stimulation of local parvalbumin-positive (PV+) interneurons in the CA1 region of the hippocampus in APP/PS1 mice. Furthermore, employing the same protocol, we successfully enhanced the performance of transgenic mice in a spatial recognition memory task. Building upon these findings, our objective is to investigate the impact of PV+ stimulation on circuit function within the CA1 region. To achieve this, we utilize the same mouse model for Aβ-pathology, specifically expressing an excitatory opsin in local PV+ interneurons and a functional Ca2+ reporter in CA1 pyramidal neurons. We subject head-fixed mice to a spatial reward-learning and memory task on a linear treadmill while simultaneously evaluating neural population coding. In this context, our goal is to identify behavioral disparities, as well as cellular and cognitive deficits, in APP/PS1 transgenic animals. Subsequently, we aim to determine if temporally and spatially controlled PV+ interneuron-mediated synchronization of population activity affects spatial representation. It will be investigated, if this modulation ultimately can be employed to ameliorate the identified deficits. Overall, the objective of this project is to establish a connection between observations associated with disturbed theta oscillations under conditions of Aβ-pathology and underlying cellular correlates.