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Wilber, A. A.

Publications and source records attributed to Wilber, A. A..

5 recordsLinked to original sources

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↗

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↗

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↗

Sex differences and effects of estrous stage on hippocampal-prefrontal theta communications

Effective communication between the mammalian hippocampus and neocortex is essential to certain cognitive-behavioral tasks critical to survival in a changing environment. Notably, functional synchrony between local field potentials (LFPs) of the ventral hippocampus (vHPC) and the medial prefrontal cortex (mPFC) within the theta band (4-12 Hz) underlies innate avoidance behavior during approach-avoidance conflict tasks in male rodents. However, the physiology of vHPC-mPFC communications in females remains unestablished. Furthermore, little is known about how mPFC subdivisions functionally interact in the theta band with hippocampal subdivisions in both sexes in the absence of task demands. Given the established roles of biological sex and gonadal hormone status on innate avoidance behaviors and neuronal excitability, here, we characterize the effects of biological sex and female estrous stage on hippocampal-prefrontal theta signaling in freely-moving female and male rats. LFPs from vHPC, dorsal hippocampus (dHPC), mPFC-prelimbic (PrL), and mPFC-infralimbic (IL) were simultaneously recorded during spontaneous exploration of a familiar arena. Data suggest that theta phase and power in vHPC preferentially synchronize with PrL; conversely, dHPC and IL preferentially synchronize. Males displayed greater vHPC-PrL theta synchrony than females, despite similar regional frequency band power and inter-regional coherence. Additionally, several significant estrous-linked changes in hippocampal-prefrontal theta dynamics were observed. These findings support the hypothesis that biological sex and female estrous stage can both affect hippocampal-prefrontal theta signaling in a familiar environment. These findings establish novel research avenues concerning sexual dimorphisms and effects of gonadal hormone status in HPC-mPFC network activity pertaining to threat evaluation biomarkers. SIGNIFICANCE STATEMENTEffective signaling between subregions of the hippocampus and the prefrontal cortex underlies several cognitive-behavioral processes necessary for survival. Theta-frequency synchrony between the local fields of the ventral hippocampus and the prefrontal cortex regulates innate avoidance behavior in male rodents. However, this circuit remains understudied in females, despite its potential utility in research modeling the neurobiology of anxiety disorders (and sex differences therein). Here, we demonstrate that both biological sex and female hormone status have multifaceted effects on hippocampal-prefrontal theta-frequency signaling in freely-moving rats during exploration of a familiar arena. These findings provide insight into how biological sex and female estrous stage shape the way in which these circuits may represent the potential for threat.

neuroscience↗

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↗