Imaging spinal cord activity in behaving animals

The spinal cord is the primary neurological link between the brain and peripheral organs. How important it is in everyday life is apparent in patients with spinal cord injury or motoneuron disease, who have dramatically reduced musculoskeletal control or capacity to sense their environment. Despite its crucial role in sensory and motor processing little is known about the cellular and molecular signaling events that underlie spinal cord function under naturalistic conditions. While genetic, electrophysiological, pharmacological, and circuit tracing studies have revealed important roles for different molecularly defined neurons, these approaches insufficiently describe the moment-to-moment neuronal and non-neuronal activity patterns that underlie sensory-guided motor behaviors in health and disease. The recent development of imaging methods for real-time interrogation of cellular activity in the spinal cord of behaving mice has removed longstanding technical obstacles to spinal cord research and allowed new insight into how different cell types encode sensory information from mechanoreceptors and nociceptors in the skin. Here, we review the current state-of-the-art in interrogating cellular and microcircuit function in the spinal cord of behaving mammals and discuss current opportunities and technological challenges.