6 research outputs found
Computational techniques to interpret the neural code underlying complex cognitive processes
Advances in large-scale neural recording technology have significantly improved the
capacity to further elucidate the neural code underlying complex cognitive processes.
This thesis aimed to investigate two research questions in rodent models. First, what
is the role of the hippocampus in memory and specifically what is the underlying
neural code that contributes to spatial memory and navigational decision-making.
Second, how is social cognition represented in the medial prefrontal cortex at the
level of individual neurons. To start, the thesis begins by investigating memory and
social cognition in the context of healthy and diseased states that use non-invasive
methods (i.e. fMRI and animal behavioural studies). The main body of the thesis
then shifts to developing our fundamental understanding of the neural mechanisms
underpinning these cognitive processes by applying computational techniques to ana lyse stable large-scale neural recordings. To achieve this, tailored calcium imaging
and behaviour preprocessing computational pipelines were developed and optimised
for use in social interaction and spatial navigation experimental analysis. In parallel,
a review was conducted on methods for multivariate/neural population analysis. A
comparison of multiple neural manifold learning (NML) algorithms identified that non linear algorithms such as UMAP are more adaptable across datasets of varying noise
and behavioural complexity. Furthermore, the review visualises how NML can be
applied to disease states in the brain and introduces the secondary analyses that
can be used to enhance or characterise a neural manifold. Lastly, the preprocessing
and analytical pipelines were combined to investigate the neural mechanisms in volved in social cognition and spatial memory. The social cognition study explored
how neural firing in the medial Prefrontal cortex changed as a function of the social
dominance paradigm, the "Tube Test". The univariate analysis identified an ensemble
of behavioural-tuned neurons that fire preferentially during specific behaviours such
as "pushing" or "retreating" for the animalâs own behaviour and/or the competitorâs
behaviour. Furthermore, in dominant animals, the neural population exhibited greater
average firing than that of subordinate animals. Next, to investigate spatial memory,
a spatial recency task was used, where rats learnt to navigate towards one of three
reward locations and then recall the rewarded location of the session. During the
task, over 1000 neurons were recorded from the hippocampal CA1 region for five rats
over multiple sessions. Multivariate analysis revealed that the sequence of neurons encoding an animalâs spatial position leading up to a rewarded location was also active
in the decision period before the animal navigates to the rewarded location. The result
posits that prospective replay of neural sequences in the hippocampal CA1 region
could provide a mechanism by which decision-making is supported
Neuronal signature of spatial decision-making during navigation by freely moving rats using calcium imaging
A challenge in spatial memory is understanding how place cell firing contributes to decision-making in navigation. A spatial recency task was created in which freely moving rats first became familiar with a spatial context over several days and thereafter were required to encode and then selectively recall one of three specific locations within it that was chosen to be rewarded that day. Calcium imaging was used to record from more than 1,000 cells in area CA1 of the hippocampus of five rats during the exploration, sample, and choice phases of the daily task. The key finding was that neural activity in the startbox rose steadily in the short period prior to entry to the arena and that this selective population cell firing was predictive of the daily changing goal on correct trials but not on trials in which the animals made errors. Single-cell and population activity measures converged on the idea that prospective coding of neural activity can be involved in navigational decision-making
Keggin-type polyoxometalates as Cu( ii ) chelators in the context of Alzheimer's disease
International audienceTwo Keggin polyoxometalates were used as new copper ligands to counteract the effects of CuII(Amyloid-ÎČ) interaction. Their ability to remove CuII from CuII(Amyloid-ÎČ), to stop CuII(Amyloid-ÎČ) induced formation of reactive oxygen species and to restore apo-like self-assembly of CuII(Amyloid-ÎČ) was shown