Mykytiuk, Vasyl; (2025) Gating of instinctive action in the midbrain. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Understanding how animals translate sensory stimuli into actions is a key challenge for neuroscience. Instinctive behaviours offer a tractable model for studying this process, as they are robust, ethologically relevant, and tightly linked to internal state and environmental context. However, how motivational signals interact with external input to guide action remains poorly understood. Here, I investigate how motivational signals and sensory cues converge to trigger instinctive behaviour, using pup retrieval in mice as a model. I show that activation of hypothalamo–midbrain projections induces retrieval, but only in the presence of retrievable objects, indicating that motivational drive alone is insufficient to trigger action. Instead, retrieval is gated by tactile input from the target object, suggesting that action initiation depends on the convergence of motivational and sensory signals. I propose a model in which sensory information is integrated with hypothalamic signals by a disinhibitory neural circuit in the midbrain that drives retrieval behaviour. I use optogenetics, chemogenetics, behavioural analysis, electrophysiology, viral tracing, and activity-dependent labelling of neurons to test this hypothesis. This study provides insights into the neural architecture and computations underlying sensorimotor transformation, emphasising the role of midbrain circuits in context-dependent behavioural gating. The findings contribute to a broader understanding of how instinctive actions are flexibly controlled through integration of internal state and external sensory cues, and may inform future work on decision-making circuits in both biological and artificial systems.

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