Introducing Optical Imaging Advances to Unravel Chronic Pain Mechanisms

The lecture will highlight how optical techniques, enabling multiscale imaging can uncover previously inaccessible principles of sensory coding. First, we know that sensory afferents transduce environmental stimuli into activity that is transmitted centrally to be decoded into corresponding sensations. Despite years of work on molecular mechanisms of transduction, culminating in this year’s Nobel prize in medicine, how natural stimuli are represented remains debated. This can only be properly addressed by monitoring the activity of large ensembles of individually identified afferents. I will describe how multiphoton imaging from hundreds of neurons in dorsal root ganglia revealed that different sensory modalities use separate coding strategies; different stimuli activate distinct combinations of diversely tuned neurons, enabling rich, yet distinct population-level information transfer. Another challenge has been understanding communication between primary afferents and spinal neurons. Recording from afferent terminals has remained extremely challenging with most mechanisms inferred from indirect or distant measurements. I will show how high resolution, random access multiphoton imaging from afferent boutons reveals a rich and diverse regulation of presynaptic activity by action potentials, excitatory and inhibitory signaling, respectively. These approaches pave the way to understanding miscoding and abnormal transmission in pathological pain conditions.