Spinal circuits for breathing

Breathing is undeniably one of the more important motor functions that we must perform. It must persist from the first breath that we take when we are born and continue until we die. Breathing must also be adapted to meet constantly changing metabolic demands, such as those imposed by movement. Therefore, the underlying neural networks that generate breathing must not only be robust, but also adaptable.

Under resting conditions, the inhalation of air into the lungs during the inspiratory phase of breathing, is exclusively driven by contraction of the diaphragm muscle, with exhalation of air during the expiratory phase produced by it’s passive relaxation. Remarkably, the respiratory system somehow knows how to predict metabolic needs that occur in response to movement. In anticipation for movement, breathing volume is increased – inspiration is facilitated through the recruitment of additional accessory respiratory muscles (external intercostals, abdominal, scapular elevator muscles). Further, expiration becomes active through the recruitment the internal intercostal and abdominal muscles. The mechanisms that underlie this feed-forward recruitment of respiratory muscles are not yet known. We think that local circuits in the cervical spinal cord might play a role in producing this activity-dependent recruitment of accessory respiratory muscles.

Leveraging tools and expertise derived from studying spinal locomotor circuits, we are working to reveal novel mechanisms that contribute to state-dependent facilitation of breathing. Current areas of study include:

Intrinsic properties shaping the recruitment of respiratory motoneurons
C boutons and cholinergic control of respiratory circuits

Breathing is impaired following spinal cord injury and in a collection of neurological disorders. Consequently, this dysfunction often leads to pneumonia or secondary cardiopulmonary complications, severely compromising quality of life. Interestingly, in many of these conditions patients present with a resting respiratory muscle activity pattern that is more typical of those found in healthy people during active states. Therefore, understanding fundamental mechanisms that underlie activity-dependent recruitment of respiratory muscles will provide insights that may lead to the development of rehabilitative strategies or therapeutic targets to attenuate respiratory dysfunction in disease.

Outputs

Calabrese, G.B.*, Broadhead, M.J., Motherwell, L., Sharples, S.A., and Miles, G.B. Cholinergic modulation of respiratory-related motor output. Society for Neuroscience. San Diego, CA, USA. Nov 2022.

Calabrese, G.B.*, Broadhead, M.J., Motherwell, L., Sharples, S.A., and Miles, G.B. Cholinergic modulation of respiratory-related motor output. International Motoneuron Society Meeting. Banff, AB, Canada, June 2022