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Browne, L. E.

Publications and source records attributed to Browne, L. E..

4 recordsLinked to original sources

A stimulus-state geometry in somatosensory cortex reorganizes during inflammatory pain

Adaptive behavior requires external input to be interpreted together with internal state and ongoing behavior. During pain, noxious somatosensory input evokes movement and arousal, and injury reshapes this relationship, yet how cortical activity organizes stimulus content with behavioral state remains unclear. In awake mice, we delivered hindpaw stimuli while tracking movement, arousal and facial expression, and studied primary somatosensory cortex (S1) using widefield and two-photon calcium imaging, single-action-potential activation of nociceptors, and S1 silencing. Here, we show that S1 neurons were broadly recruited by stimulus and state, whereas latent population dimensions carried mechanical stimulus content. Inflammatory injury caused a reorganization of S1 geometry, binding state and protective responses tighter together. Noxious heat drove S1 as strongly, but engaged mostly the state axis. S1 silencing reduced mechanical hypersensitivity, arousal, and facial expressions. S1 thus embeds mechanical input within a stimulus-state geometry, which is reorganized during inflammatory injury to support adaptation of a coordinated protective response.

neuroscience↗

Ethologically relevant behavioural assay for investigating reach and grasp kinematics during whole-body motor control in mice

Reach and grasp are critical components of skilled mammalian motor control and their detailed analysis in rodents has been key to deepening our understanding of prehension in the context of health and disease. However, most studies investigating these behaviours focus on isolating forelimb movements with little regard to the whole-body movements that are key for effective behaviour. To address this issue, we designed a novel behavioural approach to investigate reach and grasp during whole-body, vertical locomotion in mice. Using a customizable transparent climbing surface, we show that our behavioural approach can extract key kinematic features of climbing. Mouse climbing gait reflects aspects of quadrupedal locomotion, showing similar phase dependencies on increasing speed, including reduced stance (i.e. grasp) time and duty factor. Analysis of multi-limb coordination indicated that climbing revolves around anti-phasic forepaw movements with less consistency in interlimb coordination in the hindpaws. Fore- and hindpaws also differed in their reach trajectories and velocity profiles. The flexibility of this approach also allows for tailored climbing configurations, which we use to show that mice can adapt to and overcome vertical obstacles. By leveraging naturalistic climbing, our modular behavioural approach enables investigation of complex prehensile behaviours and facilitates new study into the neural circuits underlying whole-body skilled motor control.

neuroscience↗

Somatosensory stimulation in moving mice

Somatosensation connects animals to their immediate environment, shaping critical behaviors essential for adaptation, learning, and survival. Probing the relationships between somatosensory inputs and behavior in mice presents substantial challenges, primarily due to the practical difficulties of delivering stimuli to the skin during movement. To address this problem, we have developed a system for precise cutaneous stimulation of mice as they walk and run through environments. The system employs real-time body part tracking and targeted optical stimuli, offering precision while preserving the naturalistic context of the behaviors studied to overcome the traditional trade-offs between precision and animal behavior. We demonstrate the system across nociceptive testing conducted in standard small chambers to behavior in large complex environments, such as mazes. We observed that cutaneous inputs evoke rapid responses, which modify behavior when stimuli are applied during motion. This system provides a means to explore the diverse and integrative nature of somatosensation, from reflexes to decision-making, in naturalistic settings.

neuroscience↗

Scanned optogenetic control of mammalian somatosensory input to map input-specific behavioral outputs

Somatosensory stimuli guide and shape behavior, from immediate protective reflexes to longer-term learning and high-order processes related to pain and touch. However, somatosensory inputs are challenging to control in awake mammals due to the diversity and nature of contact stimuli. Application of cutaneous stimuli is currently limited to relatively imprecise methods as well as subjective behavioral measures. The strategy we present here overcomes these difficulties by achieving spatiotemporally precise, remote and dynamic optogenetic stimulation of skin by projecting light to a small defined area in freely-behaving mice. We mapped behavioral responses to specific nociceptive inputs and revealed a sparse code for stimulus intensity: using the first action potential, the number of activated nociceptors governs the timing and magnitude of rapid protective pain-related behavior. The strategy can be used to define specific behavioral repertoires, examine the timing and nature of reflexes, and dissect sensory, motor, cognitive and motivational processes guiding behavior.

neuroscience↗