Biology subjects

Gillespie, A. K.

Publications and source records attributed to Gillespie, A. K..

9 recordsLinked to original sources

bioRxiv2026

Naturalistic behavior and self-generated neural activity predictive of self-correction.

Changing ones mind -- revising a past decision independently of external cues -- can lead to better outcomes, but its neural basis remains poorly understood. We therefore developed a challenging spatial task for rats where a conflict between innate foraging biases and task rules leads to abundant, spontaneous, and characteristically corrective changes-of-mind (COMs). Neural recordings in the hippocampus, a brain region implicated in counterfactual thinking, revealed two distinct stages wherein more local representations gave way to representations of distant alternatives after animals had begun to reverse course. These representations predicted their eventual choice, and often serially encoded trial start and end locations. Our novel task paradigm reveals distinct representational phases engaged during self-correction and uncovers a rich repertoire of hippocampal spatial representations tied to behavior.

neuroscience↗

bioRxiv2025

A Semi-Automated, Parallelized, and Flexible Spatial Navigation Task for Rats

Spatial navigation tasks for rodents have been an extremely useful tool for studying cognitive processes for decades, but are often laborious to administer and sensitive to experimenter-induced variability. To address these limitations, we have developed a parallelized maze system which runs four highly flexible maze environments simultaneously with automated reward delivery, enabling reduced experimenter involvement, increased throughput, and streamlined data collection. Further, our software tracks subject performance and manages the progression through a pre-set curriculum as subjects learn, reducing experimenter error and ensuring comparable learning curves across cohorts. Equipped with IR beam-break based reward ports, peristaltic pumps for liquid reward delivery, and overhead video tracking, our current maze accessories can be flexibly reconfigured to enable a vast array of behavioral tasks and support a wide range of experimental questions. Pilot cohorts of young (4-8 month) and aged (28-32 month) male and female rats demonstrate that this apparatus enables the efficient training of a series of increasingly difficult visually cued and memory-dependent spatial navigation task variants across a wide range of performance abilities.

neuroscience↗

bioRxiv2024

Closed-loop modulation of remote hippocampal representations with neurofeedback

Humans can remember specific remote events without acting on them and influence which memories are retrieved based on internal goals. However, animal models typically present sensory cues to trigger memory retrieval and then assess retrieval based on action. Thus, it is difficult to determine whether measured neural activity patterns relate to the cue(s), the memory, or the behavior. We therefore asked whether retrieval-related neural activity could be generated in animals without cues or a behavioral report. We focused on hippocampal "place cells" which primarily represent the animals current location (local representations) but can also represent locations away from the animal (remote representations). We developed a neurofeedback system to reward expression of remote representations and found that rats could learn to generate specific spatial representations that often jumped directly to the experimenter-defined target location. Thus, animals can deliberately engage remote representations, enabling direct study of retrieval-related activity in the brain.

neuroscience↗

bioRxiv2022

Neurofeedback training can modulate task-relevant memory replay in rats

Hippocampal replay - the time-compressed, sequential reactivation of ensembles of neurons related to past experience - is a key neural mechanism of memory consolidation. Replay typically coincides with a characteristic pattern of local field potential activity, the sharp-wave ripple (SWR). Reduced SWR rates are associated with cognitive impairment in multiple models of neurodegenerative disease, suggesting that a clinically viable intervention to promote SWRs and replay would prove beneficial. We therefore developed a neurofeedback paradigm for rat subjects in which SWR detection triggered rapid positive feedback in the context of a memory-dependent task. This training protocol increased the prevalence of task-relevant replay during the targeted neurofeedback period by changing the temporal dynamics of SWR occurrence. This increase was also associated with neural and behavioral forms of compensation after the targeted period. These findings reveal short-timescale regulation of SWR generation and demonstrate that neurofeedback is an effective strategy for modulating hippocampal replay.

neuroscience↗

bioRxiv2022

Dynamic Synchronization between Hippocampal Spatial Representations and the Stepping Rhythm

Summary paragraphThe hippocampus is a vertebrate brain structure that expresses spatial representations1 and is critical for navigation2,3. Navigation in turn intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to primarily represent higher-order cognitive and locomotor variables like position, speed, and direction of movement4-7, while the limb movements that propel the animal are thought to be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem, and cerebellum8-11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at ~8 Hz during movement, matching the ~8 Hz organization of information processing in the hippocampus during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground ( plant times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations closest to the actual position of the animal, while in-between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when animals approached upcoming spatial decisions. Taken together, our results reveal profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory-motor circuits.

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bioRxiv2021

Hippocampal replay reflects specific past experiences rather than a plan for subsequent choice

Executing memory-guided behavior requires both the storage of information about experience and the later recall of that information to inform choices. Awake hippocampal replay, when hippocampal neural ensembles briefly reactivate a representation related to prior experience, has been proposed to critically contribute to these memory-related processes. However, it remains unclear whether awake replay contributes to memory function by promoting the storage of past experiences, by facilitating planning based on an evaluation of those experiences, or both. We designed a dynamic spatial task which promotes replay before a memory-based choice and assessed how the content of replay related to past and future behavior. We found that replay content was decoupled from subsequent choice and instead was enriched for representations of previously rewarded locations and places that had not been recently visited, indicating a role in memory storage rather than in directly guiding subsequent behavior.

neuroscience↗

bioRxiv2021

Dentate Gyrus and CA3 GABAergic Interneurons Bidirectionally Modulate Signatures of Internal and External Drive to CA1

Specific classes of GABAergic neurons are thought to play specific roles in regulating information processing in the brain. In the hippocampus, two major classes - parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) neurons - differentially regulate endogenous firing patterns and target different subcellular compartments of principal cells, but how these classes regulate the flow of information throughout the hippocampus is poorly understood. We hypothesized that PV+ and SST+ interneurons in the dentate gyrus (DG) and CA3 might differentially modulate CA3 patterns of output, thereby altering the influence of CA3 on CA1. We found that while suppressing either interneuron type increased DG and CA3 output, the effects on CA1 were very different. Suppressing PV+ interneurons increased local field potential signatures of coupling from CA3 to CA1 and decreased signatures of coupling from entorhinal cortex to CA1; suppressing SST+ interneurons had the opposite effect. Thus, DG and CA3 PV+ and SST+ interneurons bidirectionally modulate the flow of information through the hippocampal circuit.

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bioRxiv2020

Hippocampal replay of experience at real-world speeds

Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain "replay" of spatial trajectories at ~20x the movement speed of the animal. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here we develop a state space model that uses a combination of movement dynamics of different speeds to capture the spatial content and time evolution of replay during SWRs. Using this model, we find that the large majority of replay events contain spatially coherent, interpretable content. Furthermore, many events progress at real-world, rather than accelerated, movement speeds, consistent with actual experiences.

neuroscience↗

bioRxiv2019

Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer’s Disease Mouse Model

Alzheimers disease (AD) is characterized by progressive memory loss, and there is a pressing need to identify early pathophysiological alterations that predict subsequent memory impairment. Hippocampal sharp-wave ripples (SWRs) - electrophysiological signatures of memory reactivation in the hippocampus - are a compelling candidate for doing so. Mouse models of AD show reductions in both SWR abundance and associated slow gamma (SG) power during aging, but these alterations have yet to be directly linked to memory impairments. In aged apolipoprotein E4 knock in (apoE4-KI) mice - a model of the major genetic risk factor for AD - we found that reduced SWR abundance and associated CA3 SG power predicted spatial memory impairments measured 1-2 months later. Importantly, SWR-associated CA3 SG power reduction in young apoE4-KI mice also predicted spatial memory deficits measured 10 months later. These results establish features of SWRs as potential functional biomarkers of memory impairment in AD.

neuroscience↗