Parkes, Isobel; (2024) Somatosensory Stimulation during Exploration: An Approach to Study How Pain is Embedded within Complex Behaviour. Doctoral thesis (Ph.D), UCL (University College London).

Text Isobel_Parkes_IsobelParkes_ThesisCorrections.pdf - Other Access restricted to UCL open access staff until 1 September 2025. Download (98MB)

Abstract

Somatosensation connects animals to their environment, influencing essential behaviours for adaptation, learning, and survival. Traditional methods to study somatosensation, pain, and behaviour typically involve direct physical contact, where stimuli are manually applied. Unlike visual, olfactory, and auditory systems, which can use remote stimuli, delivering somatosensory inputs to moving mice presents a significant challenge. To address this, this thesis introduces a novel technology enabling context-dependent somatosensory stimulation in unrestrained, moving mice. This approach employs real-time keypoint tracking and targeted optical stimulation, maintaining natural behaviours while offering precision and control. I demonstrated the system’s flexibility by targeting stimuli with high accuracy in both static and moving mice across varied environments. First, I developed a method for multi-animal nociceptive testing. Infrared and optogenetic laser stimuli elicited immediate nocifensive and coping behaviours, which could be mapped. This strategy examines rapid movements within complex behaviours, offering insights into nociception and potential for analgesic development for chronic pain. Next, I studied exploratory behaviour under phasic and tonic pain conditions. Phasic nociceptive inputs during open field exploration evoked rapid evaluative behaviours, disrupted goal-directed movement in a maze when stimuli were applied during running, but overall exploration was not altered in mice with or without ongoing pain, suggesting a preference for exploration and reward-seeking over pain avoidance. Finally, I investigated how persistent pain impacts adaptive behaviour in response to threat, focusing on the primary somatosensory cortex (S1). Defensive behaviours were heightened in mice with persistent pain. Inhibiting S1 with optogenetic and chemogenetic approaches heightened defensive behaviours in the absence of ongoing pain, revealing broader functions within defensive circuitry. In summary, this thesis explores how pain is embedded within complex behaviours in naturalistic settings. Delivering somatosensory stimuli to freely behaving mice can provide insights into the diverse roles of somatosensation—from reflexes to decision-making and adaptive behaviour—in naturalistic environments.

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