Physiology seminars

Each day we experience myriad somatosensory stimuli: hugs from loved ones, warm showers, a mosquito bite, and sore muscles after a workout. These tactile, thermal, itch, and nociceptive signals are detected by peripheral sensory neuron terminals distributed throughout our body, propagated into the spinal cord, and then transmitted to the brain through ascending spinal pathways. Primary sensory neurons that detect a wide range of somatosensory stimuli have been identified and characterized. In contrast, very little is known about how peripheral signals are integrated and processed within the spinal cord and conveyed to the brain to generate somatosensory perception and behavioral responses. We tackled this question by developing new mouse genetic tools to define projection neuron (PN) subsets of the anterolateral pathway, a major ascending spinal cord pathway, and combining these new tools with advanced anatomical, physiological, and behavioral approaches. We found that Gpr83+ PNs, a newly identified subset of spinal cord output neurons, and Tacr1+ PNs are largely non-overlapping populations that innervate distinct sets of subnuclei within the lateral parabrachial nucleus (PBNL) of the pons in a zonally segregated manner. In addition, Gpr83+ PNs are highly sensitive to cutaneous mechanical stimuli, receive strong synaptic inputs from primary mechanosensory neurons, and convey tactile information bilaterally to the PBNL in a non-topographically organized manner. Remarkably, Gpr83+ mechanosensory limb of the anterolateral pathway controls behaviors associated with different hedonic values (appetitive or aversive) in a scalable manner. This is the first study to identify a dedicated spinal cord output pathway that conveys affective touch signals to the brain and to define parallel ascending circuit modules that cooperate to convey tactile, thermal and noxious cutaneous signals from the spinal cord to the brain. This study has also revealed exciting new therapeutic opportunities for developing treatments for neurological disorders associated with pain and affective touch.

The Ca2+ modulated pulsatile secretions of glucagon and insulin by pancreatic α and β cells play a key role in glucose metabolism and homeostasis. However, how different types of cells in the islet couple and coordinate to give rise to various Ca2+ oscillation patterns and how these patterns are being tuned by paracrine regulation are still elusive. Here we developed a microfluidic device to facilitate long-term recording of islet Ca2+ activity at single cell level and found that islets show heterogeneous but intrinsic oscillation patterns. The α and β cells in an islet oscillate in antiphase and are globally phase locked to display a variety of oscillation modes. A mathematical model of islet oscillation maps out the dependence of the oscillation modes on the paracrine interactions between α and β cells. Our study reveals the origin of the islet oscillation patterns and highlights the role of paracrine regulation in tuning them.

Many visual systems can process information in dynamically changing environments. In general, visual perception scales with changes in the visual stimulus, or contrast, irrespective of background illumination. This is achieved by adaptation. However, visual perception is challenged when adaptation is not fast enough to deal with sudden changes in overall illumination, for example when gaze follows a moving object from bright sunlight into a shaded area. We have recently shown that the visual system of the fly found a solution by propagating a corrective luminance-sensitive signal to higher processing stages. Using in vivo two-photon imaging and behavioural analyses we showed that distinct OFF-pathway inputs encode contrast and luminance. The luminance-sensitive pathway is particularly required when processing visual motion in contextual dim light, when pure contrast sensitivity underestimates the salience of a stimulus. Recent work in the lab has addressed the question how two visual pathways obtain such fundamentally different sensitivities, given common photoreceptor input. We are furthermore currently working out the network-based strategies by which luminance- and contrast-sensitive signals are combined to guide appropriate visual behaviour. Together, I will discuss the molecular, cellular, and circuit mechanisms that ensure contrast computation, and therefore robust vision, in fast changing visual scenes.