Techniques and Approaches: From Molecules to Circuits to Whole Animal Physiology
The goal of the Crone Lab is to develop novel treatment strategies targeting neural circuits to restore breathing following injury or disease. The lab uses a variety of techniques to identify neurons important for the control of respiratory muscles and identify molecules in those neurons that have the potential to serve as drug targets to improve breathing.
We use mouse models of disease (ALS, muscular dystrophy, epilepsy) or injury (spinal cord injury) to investigate how breathing is altered and/or how the nervous system compensates for impaired respiratory function. A combination of transgenic mouse and viral tools such as chemogenetics (e.g., DREADDs), optogenetics, conditional knock-outs, neuron ablation, etc. are used to alter the activity or functions of specific classes of neurons in order to determine how they contribute to the control of respiratory muscles in healthy animals as well as following disease or injury.
We measure respiration using electromyography (EMG) to measure the activity of respiratory muscles and/or plethysmography to assess ventilation in awake or anesthetized mice. RNA sequencing is used to better understand the diversity of gene expression within spinal neurons, determine how they are affected by disease and injury at the molecular level, and to identify potential drug targets to improve breathing.
Our current research focuses on understanding how spinal neurons could be targeted to restore breathing after spinal cord injury, how accessory respiratory muscles are used to compensate for disease and injury, and how we might prevent sudden death in epilepsy (SUDEP).