Somatosensory stimuli guide and shape behavior, from immediate protective reflexes to longer-term learning and higher-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, achieving 'remote touch' with spatiotemporally precise and dynamic optogenetic stimulation by projecting light to a small defined area of skin. We mapped behavioral responses in freely behaving mice with specific nociceptor and low-threshold mechanoreceptor inputs. In nociceptors, sparse recruitment of single-action potentials shapes rapid protective pain-related behaviors, including coordinated head orientation and body repositioning that depend on the initial body pose. In contrast, activation of low-threshold mechanoreceptors elicited slow-onset behaviors and more subtle whole-body behaviors. 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.
Keywords: behavior; machine vision; mouse; neuroscience; optogenetics; pain; somatosensation; touch.
To safely navigate their world, animals need to be able to tell apart a gentle touch from an eye-watering pinch, detect cold water or sense the throbbing pain stemming from an infected cut. These ‘somatic’ sensations are relayed through thousands of nerve endings embedded in the skin and other tissues. Yet the neurological mechanisms that underpin these abilities are complex and still poorly understood. Indeed, these nerve endings can be stimulated by extreme temperatures, harmful chemicals, friction or even internal signals such as inflammation. One event can also recruit many different types of endings: a cut for example, will involve responses to mechanical pressure, tissue damage and local immune response. To disentangle these different actors and how they affect behavior, scientists need to develop approaches that allow them to deliver specific stimuli with increased precision, and to monitor the impact on an animal. To achieve this goal, Schorscher-Petcu et al. used mice in which blue light could trigger specific types of nerve endings. For instance, depending on the genetic background of the animals, a laser could either activate nerve endings involved in pain or gentle touch. Crucially, this could be done from a distance by beaming light with exquisite precision onto the paws of the mice without physically touching or disturbing the animals. How the mice responded could then be observed without any interference. Their behavior was analyzed using a combination of high-speed videos, computer-driven recording systems, and machine learning. This revealed subtle changes in behavior that had not been detected before, spotting microscopic movements of the stimulated paw and mapping simultaneous whole-body movements such as changes in posture or head orientation. The approach therefore allows scientists to assess the impact of touch, pain or temperature sensation in freely behaving mice. It could also be harnessed to develop much needed treatments against chronic pain.
© 2021, Schorscher-Petcu et al.