Biology subjects

Moseley, S. C.

Publications and source records attributed to Moseley, S. C..

5 recordsLinked to original sources

bioRxiv2024

Resting After Learning Facilitates Memory Consolidation and Reverses Spatial Reorientation Impairments in 'New Surroundings' in 3xTg-AD Mice

Sleep is an essential component of productive memory consolidation and waste clearance, including pathology associated with Alzheimers disease (AD). Facilitation of sleep decreases A{beta} and tau accumulation and is important for the consolidation of spatial memories. We previously found that 6-month female 3xTg-AD mice were impaired at spatial reorientation. Given the association between sleep and AD, we assessed the impact of added rest on impaired spatial reorientation that we previously observed. We randomly assigned 3xTg-AD mice to a rest (n=7; 50 min pre- & post-task induced rest) or a non-rest group (n=7; mice remained in the home cage pre- & post-task). Mice in both groups were compared to non-Tg, age-matched, non-rest controls (n=6). To confirm that our sleep condition induced sleep, we performed the same experiment with rest sessions for both 3xTg-AD and non-Tg mice (n=6/group) implanted with recording electrodes to capture local field potentials (LFPs), which were used to classify sleep states. Markers of pathology were also assessed in the parietal-hippocampal network, where we previously showed pTau positive cell density predicted spatial reorientation ability (pTau, 6E10, M78, and M22). However, we found that 3xTg-AD rest mice were not impaired at spatial reorientation compared to non-Tg mice and performed better than 3xTg-AD non-rest mice (replicating our previous work). This recovered behavior persisted despite no change in the density of pathology positive cells. Thus, improving sleep in early stages of AD pathology offers a promising approach for facilitating memory consolidation and improving cognition.

neuroscience↗

bioRxiv2024

A Hippocampal-parietal Network for Reference Frame Coordination

Navigating space and forming memories based on spatial experience are crucial for survival, including storing memories in an allocentric (map-like) framework and conversion into body-centered action. The hippocampus and parietal cortex (PC) comprise a network for coordinating these reference frames, though the mechanism remains unclear. We used a task requiring remembering previous spatial locations to make correct future action and observed that hippocampus can encode the allocentric place, while PC encodes upcoming actions and relays this to hippocampus. Transformation from location to action unfolds gradually, with Came From signals diminishing and future action representations strengthening. PC sometimes encodes previous spatial locations in a route-based reference frame and conveys this to hippocampus. The signal for the future location appears first in PC, and then in hippocampus, in the form of an egocentric direction of future goal locations, suggesting egocentric encoding recently observed in hippocampus may originate in PC (or another "upstream" structure). Bidirectional signaling suggests a coordinated mechanism for integrating map-like, route-centered, and person-centered spatial reference frames at the network level during navigation.

neuroscience↗

bioRxiv2024

Rescuing impaired hippocampal-cortical interactions and spatial reorientation learning and memory during sleep in a mouse model of Alzheimer's disease using hippocampal 40 Hz stimulation

Summary/AbstractIn preclinical Alzheimers disease (AD), spatial learning and memory is impaired. We reported similar impairments in 3xTg-AD mice on a virtual maze (VM) spatial-reorientation-task that requires using landmarks to navigate. Hippocampal (HPC)-cortical dysfunction during sleep (important for memory consolidation) is a potential mechanism for memory impairments in AD. We previously found deficits in HPC-cortical coordination during sleep coinciding with VM impairments the next day. Some forms of 40 Hz stimulation seem to clear AD pathology in mice, and improve functional connectivity in AD patients. Thus, we implanted a recording array targeting parietal cortex (PC) and HPC to assess HPC-PC coordination, and an optical fiber targeting HPC for 40 Hz or sham optogenetic stimulation in 3xTg/PVcre mice. We assessed PC delta waves (DW) and HPC sharp wave ripples (SWRs). In sham mice, SWR-DW cross-correlations were reduced, similar to 3xTg-AD mice. In 40 Hz mice, this phase-locking was rescued, as was performance on the VM. However, rescued HPC-PC coupling no longer predicted performance as in NonTg animals. Instead, DWs and SWRs independently predicted performance in 40 Hz mice. Thus, 40 Hz stimulation of HPC rescued functional interactions in the HPC-PC network, and rescued impairments in spatial navigation, but did not rescue the correlation between HPC-PC coordination during sleep and learning and memory. Together this pattern of results could inform AD treatment timing by suggesting that despite applying 40 Hz stimulation before significant tau and amyloid aggregation, pathophysiological processes led to brain changes that were not fully reversed even though cognition was recovered. Significance StatementOne of the earliest symptoms of Alzheimers disease (AD) is getting lost in space or experiencing deficits in spatial navigation, which involve navigation computations as well as learning and memory. We investigated cross brain region interactions supporting memory formation as a potential causative factor of impaired spatial learning and memory in AD. To assess this relationship between AD pathophysiology, brain changes, and behavioral alterations, we used a targeted approach for clearing amyloid beta and tau to rescue functional interactions in the brain. This research strongly connects brain activity patterns during sleep to tau and amyloid accumulation, and will aid in understanding the mechanisms underlying cognitive dysfunction in AD. Furthermore, the results offer insight for improving early identification and treatment strategies.

animal behavior and cognition↗

bioRxiv2023

An Integrated Platform for in vivo Electrophysiology in Spatial Cognition Experiments

Spatial cognition research requires behavioral paradigms that can distinguish between different navigational elements, such as allocentric (map-like) navigation and egocentric (e.g., body centered) navigation. To fill this need, we developed a flexible experimental platform that can be quickly modified without the need for significant changes to software and hardware. In this paper, we present this inexpensive and flexible behavioral platform paired with software which we are making freely available. Our behavioral platform serves as the foundation for a range of experiments, and though developed for assessing spatial cognition, it also has applications in the non-spatial domain of behavioral testing. There are two components of the software platform, Maze and Stim Trigger. Both programs can work in conjunction with electrophysiology acquisition systems, allowing for precise time stamping of neural events with behavior. The Maze program includes functionality for automatic reward delivery based on user defined zones. Stim Trigger permits control of brain stimulation via any equipment that can be paired with an Arduino board. We seek to share our software and leverage the potential by expanding functionality in the future to meet the needs of a larger community of researchers. Significance StatementThis paper presents an innovative and cost-effective behavioral platform designed to distinguish between different navigational elements, addressing the crucial need for better spatial cognition research paradigms. The platforms flexibility allows for quick modifications without major software or hardware changes. Additionally, the freely available software, comprising Maze and Stim Trigger components, enables precise time stamping of neural events with behavior, while facilitating automatic reward delivery and brain stimulation control. Beyond spatial cognition assessment, the platforms adaptability extends to non-spatial behavioral testing. By openly sharing this software, the authors aim to foster collaboration and encourage future developments, promoting its application to a broader community of researchers. This platform represents a significant advancement in spatial cognition research and behavioral experimentation methods.

animal behavior and cognition↗

bioRxiv2018

Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer’s Disease

In early Alzheimers disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost in new surroundings is one of the first impairments to emerge in AD. It is possible that getting lost in new surroundings represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not male, 3xTg-AD mice were impaired. Male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks.

neuroscience↗