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The role of the ventral hippocampus in probabilistic reversal learning in mice

Mishchanchuk, Karyna; (2023) The role of the ventral hippocampus in probabilistic reversal learning in mice. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Recent evidence suggests that during decision making in uncertain dynamic environments humans and mice often rely on hidden state inference to guide their behaviour. Midbrain dopamine dynamics were also proposed to reflect such use of hidden states. We hypothesised that hippocampus might be involved in hidden state inference and that it may provide state-based predictions to the dopaminergic midbrain. However, the exact contribution of hippocampus and the circuit basis of these computations are not fully understood. To investigate this, we used a probabilistic reversal task in mice, a behavioural paradigm in which for optimal performance it is necessary to continuously integrate past trial outcomes to infer the identity of the currently most rewarding choice. Probing mouse behaviour with computational modelling, we found that it was best fit by either value updating with forgetting or state inference models. However, by recording dopamine release in the nucleus accumbens (NAc) during the task, we found that it was most strongly predicted by error associated with the hidden state inference. We also found that inactivation of ventral hippocampus (vH) rendered the dopamine release more aligned with predictions from the value-based strategy, suggesting role of vH in hidden state inference. We subsequently identified that state-based predictions from vH may reach the ventral tegmental area via disynaptic projection pathways though prefrontal cortex (PFC) and NAc. Using in vivo optogenetics we found that NAc-projecting vH neurons were specifically implicated in outcome-based updating, while PFC projection was involved in the outcome-independent action-selection. Overall, in this thesis I explored the strategies and neural basis of flexible decision making in mice. Our findings provide evidence for a role of vH in hidden state inference and the circuit basis for its influence over midbrain dopamine dynamics during probabilistic reversal behaviour.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of the ventral hippocampus in probabilistic reversal learning in mice
Language: English
Additional information: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10168954
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