Wiring and Function of Somatosensory Circuits

Specialized subsets of primary sensory neurons innervating different body tissues detect and transduce different environmental cues into itch, touch, temperature or pain information. When these signals eventually reach the brain, they generate the sensory percept and evoke the convenient physiological and behavioural responses for the survival of the animal. On its way to the brain, this sensory information undergoes an initial processing at the spinal cord. In healthy individuals, local excitatory and inhibitory spinal cord interneurons form modality specific processing microcircuits. These circuits dynamically tune down or amplify the sensory signals in response to other sensory modalities or to brain descending signals. However, in certain pathologies like nerve injury or in different inflammatory conditions, the normal processing at the spinal cord is altered and unconventional maladaptive circuits are wired up, resulting in chronic pain and itch. Due to the intrinsic complexity of the spinal cord circuitry, and the lack of an appropriate tool set for capturing and interrogating the spinal cord neuronal ensembles in behaving animals, our knowledge on the cellular and molecular substrates that constitute the sensory microcircuits and facilitate maladaptive changes are still largely unknown.

The overarching goal of the group is to define the spinal circuits associated with pain signals, to better understand processing alterations associated with chronicity, age and gender. In addition, we are trying to understand how different sensory modalities influence each other, as in the case of cold alleviating pain or itch, with the final aim of exploring and developing therapeutical strategies to improve quality of live in patients suffering from chronic itch and pain.

To achieve this objective, we seek to characterize the molecular identity and intrinsic electrophysiological properties of the interneurons that constitute these sensory microcircuits, as well as defining the changes they undergo in pathological states. We combine the development of minimally-invasive circuit marking and manipulation technologies with other state-of-the-art techniques, including different viral tracing approaches, optogenetics, whole spinal cord imaging and single-nucleus sequencing with well-stablished electrophysiological techniques.