Developing a System to Investigate Age-Related Differences in the Real-Time Utilization of Dynamically Changing External Cues during Navigation

Abstract

Successful navigation depends critically upon two broad categories of sensory information, environmental (allothetic) and self-motion (idiothetic). Both the hippocampus and the medial portion of the entorhinal cortex (MEC) are critical for spatial navigation and contain functionally distinct sub-networks of spatially-modulated cells. These cells are characterized by their tuning to different spatial sensory-perceptual features of the environment and all utilize both allothetic and idiothetic cues to anchor and update their spatial firing to generate a comprehensive and dynamic representation of space. As with older adults, aged rats show pronounced impairments on a number of different spatial navigation tasks and these impairments are accompanied by a bias toward relying on egocentric over allocentric navigation strategies. Similarly, the hippocampus and MEC are also highly susceptible to age-associated changes. The influence visual allothetic cues exert on hippocampal place cell spatial tuning is diminished and delayed in aged animals. Two plausible and non-exclusive explanations that could account for these age-related alterations in allothetic processing are 1) circuit disruptions caused by known age-related functional and anatomical changes in the entorhinal-hippocampal processing pathway or 2) degraded sensory-perceptual information resulting from well-established age-related deficits across multiple sensory domains. Either of these possibilities could have the effect of either slowing allothetic cue processing or weakening the ability of these cues to influence firing field alignment. Within this context, this thesis was conceived with the aim of investigating the degree and timing with which young and aged animals utilize allothetic and idiothetic feedback to update their internal representation of space and calibrate their behavioral output. A large focus of this thesis is given to the incremental design and piloting of a number of novel technologies. Foremost among the methodological contributions of this study is the development of an augmented reality behavioral apparatus, termed the Instantaneous Cue Rotation (ICR) arena, which utilizes projected visual cues to allow for rapid remote control of all symmetry breaking visual features in the environment as rats actively engage in a visual-cue based goal navigation task. The results of extensive behavioral piloting of old and young rats validate both the ICR rotation manipulation as well as the mobile reward delivery system. This system traverses the track in tandem with the rat, enabling food based spatial reinforcement while preventing food-related olfactory cues from becoming associated with any specific location. In parallel with this work, microdrive technology was developed to enable simultaneous recording from both MEC and CA1 which is discussed along with results from single-region hippocampal and MEC implanted rats assessed in the context of a cue rotation manipulation conceptually similar to the that of the ICR. Finally, the results of the behavioral study suggest that in young rats the cue rotation exerts reliable but incomplete control over running behavior. In aged rats, by comparison, the cues exert an overall less pronounced influence on running behavior, consistent with known age-related deficits in allothetic processing. When assessed on a lap-by-lap basis, it was found that the behavior of both young and aged rats became progressively more aligned with the cues over the first few laps following cue rotation. These findings suggest a progressive realignment of behavior from an egocentric to an allocentric reference frame which is reminiscent of the reported progressive realignment of place field firing in response to conflicting spatial feedback.