Large scale optical imaging of peripheral and central nociceptive pathways in vivo

抄録

Greater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging in the central nervous system. However, this has only recently been applied to the study of pain. To assess large networks of hundreds of sensory neurons simultaneously, we developed a method to selectively label these neurons with GCaMP6s and to visualise their functional responses in vivo to peripheral stimulation. We show that this technique is able to monitor simultaneously the activity of hundreds of sensory neurons. It is sensitive enough to detect single action potentials in most cells and also provides a proxy for the amount of firing within the physiological range. We have characterised responses of cells to mechanical, thermal and chemical stimulation. The assessment of multiple sensory neurons simultaneously within a physiological setting and at high spatial and temporal resolution provides a novel method to address 'population' based questions not amenable to traditional recording techniques. We have also recently found that we can monitor the activity of some central circuits responding to noxious stimuli. In particular we have studied the responses of neurons of lamina I of the spinal cord that project to supraspinal sites. We know that functionally, these neurones play an essential role in signalling pain related to both chronic inflammatory and neuropathic disorders. Here I will review our recent work studying populations of these cells again using GCaMP as a reporter.

The scale and sensitivity of these optical techniques provide many opportunities to better understand the neuronal circuitry underpinning pain states.