Abstract

Respiratory motor failure is the leading cause of death in spinal cord injury (SCI). Cervical injuries disrupt connections between brainstem neurons that are the primary source of excitatory drive to respiratory motor neurons in the spinal cord and their targets. In addition to direct connections from bulbospinal neurons, respiratory motor neurons also receive excitatory and inhibitory inputs from propriospinal neurons, yet their role in the control of breathing is often overlooked. In this review, we will present evidence that propriospinal neurons play important roles in patterning muscle activity for breathing. These roles likely include shaping the pattern of respiratory motor output, processing and transmitting sensory afferent information, coordinating ventilation with motor activity, and regulating accessory and respiratory muscle activity. In addition, we discuss recent studies that have highlighted the importance of propriospinal neurons for recovery of respiratory muscle function following SCI. We propose that molecular genetic approaches to target specific developmental neuron classes in the spinal cord would help investigators resolve the many roles of propriospinal neurons in the control of breathing. A better understanding of how spinal circuits pattern breathing could lead to new treatments to improve breathing following injury or disease.

Highlights

  • Respiratory failure is the leading cause of death in spinal cord injury (SCI) (Berlly and Shem, 2007; Berlowitz et al, 2016)

  • There is convincing evidence that propriospinal neurons help pattern the activity of respiratory muscles in order to meet the needs of the organism

  • There is mounting evidence that spinal circuitry is altered after disease and injury, that spinal network plasticity contributes to recovery, and that propriospinal neurons are an attractive therapeutic target to improve respiratory motor function

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Summary

INTRODUCTION

Respiratory failure is the leading cause of death in spinal cord injury (SCI) (Berlly and Shem, 2007; Berlowitz et al, 2016). Since respiratory motor neurons receive excitatory and inhibitory inputs from propriospinal neurons, spinal circuits may serve as substrates to improve breathing following injury (Lane, 2011; Lee and Fuller, 2011; Marchenko et al, 2015; Zholudeva et al, 2018b). For the purposes of this review, we refer to propriospinal neurons as neurons whose cell bodies are located in the spinal cord but do not project outside the central nervous system. They may have short segmental projections, long multi-segmental spinal projections, and/or projections. We will discuss how modern tools to label or manipulate specific developmental neuron classes could help investigators further probe the role of propriospinal neurons in the control of breathing

PROPRIOSPINAL NEURONS PATTERN RESPIRATORY MOTOR ACTIVITY
Propriospinal Neurons Shape the Pattern of Respiratory Motor Output
Propriospinal Neurons Process and Transmit Sensory Afferent Information
Propriospinal Neurons Help Coordinate Ventilation and Motor Activity
Propriospinal Neurons Regulate Accessory Respiratory Muscle Activity
Developmental Neuron Classes Perform Distinct Functions
Potential Roles for Developmental Neuron Classes in Breathing
CONCLUSIONS
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