Biology subjects

Shipley, S.

Publications and source records attributed to Shipley, S..

2 recordsLinked to original sources

bioRxiv2024

Disordered Hippocampal Reactivations Predict Spatial Memory Deficits in a Mouse Model of Alzheimer's Disease

Alzheimers disease (AD) is characterised by progressive memory decline associated with hippocampal degeneration. However, the specific physiological mechanisms underlying hippocampal dysfunction in AD remain poorly understood and improved knowledge may aid both diagnosis and help identify new avenues for therapeutic intervention. We investigated how disruptions in hippocampal reactivations relate to place cell stability and spatial memory deficits in an AD mouse model. Using the APP knock-in mouse model NL-G-F, we conducted simultaneous behavioural and electrophysiological recordings in a radial arm maze. NL-G-F mice exhibited significant impairments in memory performance, demonstrated by an increased propensity to revisit arms, compared to wild-type controls. These memory deficits were associated with a reduction in the stability of hippocampal place cells, which occurred over short timescales and was accentuated across rest. While the rate of hippocampal reactivation events during rest was unchanged, the structure of these events was significantly degraded in NL-G-F mice. The decreased structure of reactivations was predictive of decreased stability in place cell firing. These findings suggest that disrupted reactivation sequences may act as a mechanism of memory disorder in AD.

neuroscience↗

bioRxiv2018

Entorhinal neurons exhibit cue locking in rodent VR

The regular firing pattern exhibited by medial entorhinal (mEC) grid cells of locomoting rodents is hypothesized to provide spatial metric information relevant for navigation. The development of virtual reality (VR) for head-fixed mice confers a number of experimental advantages and has become increasingly popular as a method for investigating spatially-selective cells. Recent experiments using 1D VR linear tracks have shown that some mEC cells have multiple fields in virtual space, analogous to grid cells on real linear tracks. We recorded from the mEC as mice traversed virtual tracks featuring regularly spaced repetitive cues and identified a population of cells with multiple firing fields, resembling the regular firing of grid cells. However, further analyses indicated that many of these were not, in fact, grid cells because: 1) When recorded in the open field they did not display discrete firing fields with six-fold symmetry; 2) In different VR environments their firing fields were found to match the spatial frequency of repetitive environmental cues. In contrast, cells identified as grid cells based on their open field firing patterns did not exhibit cue locking. In light of these results we highlight the importance of controlling the periodicity of the visual cues in VR and the necessity of identifying grid cells from real open field environments in order to correctly characterise spatially modulated neurons in VR experiments.

neuroscience↗