Escape Decision Neurons - Mouse Midbrain


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Decision-making and action selection

Reaching a decision requires interpreting information about the current environment and comparing available actions. But how does the brain transform information about the world into purposeful actions? 

At SWC, we aim to establish a theoretical framework for how decisions are made and map this framework onto computations in neural circuits.

In some cases, evolution has resulted in sensory stimuli having intrinsic values that directly select appropriate actions. For example, the smell of pups in rodents drives mothers to initiate maternal behaviours. Similarly, when a dark shadow appears overhead, rodents initiate appropriate defensive behaviours such as escaping or freezing. 

In contrast to these innate behaviours, the brain can also learn the value of stimuli and resultant actions, thereby allowing it to generate adaptive behavioural responses through experience. At SWC we are testing the hypothesis that the basal ganglia are the key structures supporting this process via reinforcement leaning, enabling the coupling of sensory context to specific actions.

We are also exploring how the brain guides behavioural choices under conditions of uncertainty, such as when only partial sensory evidence is available. We know that such decisions must rely on combining prior knowledge with existing sensory input, but where and how this is achieved in the brain is not currently well understood.

Current research

The Branco lab are working to determine the biophysical and circuit mechanisms which enable the integration of sensory evidence of threat into escape decisions. They are also looking to
describe how knowledge of the environment and the internal state modulate the escape response. 

As context and/or prior experience can shape the decision to engage in defensive behaviour, the Branco, Hofer, Stephenson-Jones and Margrie labs are also working to determine the contribution of inhibitory circuits in the thalamus and basal ganglia in adaptive regulation of escape. 

The Isogai lab is studying how the amygdala orchestrates specific innate social behaviours. Furthermore, the Duan and Erlich labs are studying the neural mechanisms of social decisions by training animals in ethologically relevant foraging tasks that can be quantified in a game-theoretic framework. Their aim is to discover where and how information about the other player is represented in the brain and how this information is integrated with reward information to guide choice behaviours in a social context.

The Duan lab is researching risky decisions and “when does it pay to gamble”. The team are using mouse models of risk decision making to study how interconnected cortico-subcortical networks allow the brain to compute expected value, to compare the values of different options, to select an option and transform that selection into an action. 

Furthermore, the Erlich lab is working to understand the neurobiology of economic decisions, such as choosing between £10 today and £20 in a year. The team are training humans in non-verbal tasks, to bridge the gap between human and animal studies.

The Stephenson-Jones and Mrsic-Flogel labs are collaborating to determine how sensory representations are used to drive specific, learned actions in the basal ganglia, and to identify circuit mechanisms for learning and implementation of this sensorimotor transformation, using chronic recordings and activity manipulations in different classes of cortico-striatal projection neurons.

Furthermore, a collaboration between the Burgess*, Stephenson-Jones and Branco labs is testing models of hippocampal-striatal interactions linking neural responses to navigation and planning and also how ‘model-based’ and ‘model-free’ reinforcement learning combine. 

The Akrami and Mrsic-Flogel labs are also working closely with the Burgess lab and DeepMind to reveal the mechanisms by which prior knowledge and sensory evidence are integrated into the process of selecting appropriate actions. 

The Akrami lab are working to uncover the circuit mechanisms underlying the joint representation of the interaction of current sensory evidence and recent sensory history by the parietal cortex. 

The Mrsic-Flogel lab are testing the hypothesis that premotor cortex integrates decision-relevant information from sensory and parietal cortical areas to initiate action selection, using novel decision-making behavioural paradigms with targeted activity measurements and perturbations of identified neuronal populations in candidate brain regions. 

The teams are also collaborating with GCNU to generate a model that explains animals’ decision process, by validating against trial-by-trial performance in the task on one hand and by testing how accurately it predicts the decision-related neural activity on the other.

*Neil Burgess is part of our affiliates programme at SWC.