Pre-phrenic interneurons: Characterization and role in phrenic pattern formation and respiratory recovery following spinal cord injury

Ghali, Michael George Zaki; Britz, Gavin W.; Lee, Kun‐Ze

doi:10.1016/j.resp.2018.09.005

Cited by 27 publications

(10 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mammalian breathing sustains life by mediating gas exchange (Ausborn et al, 2018; Marchenko, Ghali, & RogersRogers, 2012, 2016; Molkov, Rubin, Rybak, & Smithet, 2017; Zaki Ghali et al, 2019). Inspiration introduces oxygen‐saturated ambient air to the bronchioles and alveoli and dilutes bronchiolar and alveolar carbon dioxide concentration; expiration expels the alveolar mixture generated by inhalation.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Midbrain control of breathing and blood pressure: The role of periaqueductal gray matter and mesencephalic collicular neuronal microcircuit oscillators

Ghali

2020

Eur J of Neuroscience

View full text Add to dashboard Cite

Neural circuitry residing within the medullary ventral respiratory column nuclei and dorsal respiratory group interacts with the Kölliker-Fuse and medial parabrachial nuclei to generate the core breathing rhythm and pattern during rest. Triphasic eupnea consists of inspiratory [I], post-inspiratory [post-I], and late-expiratory [E2] phases. Mesencephalic zones exert modulatory influences upon respiratory rhythm-generating circuitry, sympathetic oscillators, and cardiovagal premotoneurons. The earliest evidence supporting the existence of midbrain control of breathing derives from studies conducted by Martin and Booker in 1878. These authors demonstrated electrical stimulation of the deep layers of the mesencephalic colliculi in the rabbit augmented ventilation and sequentially elicited chest wall tremors and tetany. Investigations conducted during the past several decades would demonstrate stimulation of distributed zones within the midbrain reticular formation elicits starkly disparate effects upon respiratory phase switching. Schmid, Böhmer, and Fallert demonstrated electrical stimulation of the nucleus rubre and emanating axon bundles alternately elicits or inhibits the activity of medullary expiratory-or inspiratory-related units and phrenic nerve discharge with differential latency. A series of studies would later indicate the red nucleus mediates hypoxic ventilatory depression. Periaqueductal gray matter neurons exhibit extensive interconnectivity with suprabulbar, brainstem, and spinal cord zones aptly positioning these units to modulate breathing, autonomic outflow, nociception locomotion, micturition, and sexual behavior. Experimental stimulatory activation of the tectal colliculi and periaqueductal gray matter via electrical current

show abstract

Section: Introductionmentioning

confidence: 99%

Retracted: Midbrain control of breathing and blood pressure: The role of periaqueductal gray matter and mesencephalic collicular neuronal microcircuit oscillators

Ghali

2020

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…These task-and background modulation-dependent choices of stimulation frequency for locomotor function paradigms suggest a need for continued investigation of frequency-dependent effects in the respiratory system. This is particularly important given the fact that there is a brain stem-regulated frequency component in shaping the breathing pattern that is separate from potential sites of modulation such as prephrenic cervical interneuron (310,311), phrenic afferent (166), and propriospinal (70) inputs. Indeed, reports of endogenous cervical neuromodulation (with its own frequency component) of phrenic motor neurons are conflicting, with some suggesting background neuromodulation via excitatory (83), inhibitory (312), or a combination thereof (313), given that suprathreshold stimulation can evoke phase-dependent differential evoked responses.…”

Section: The Effects Of Stimulation Parameters On Ees Outcomesmentioning

confidence: 99%

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

Malone

Nosacka

Nash

et al. 2021

Journal of Neurophysiology

View full text Add to dashboard Cite

Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity including a brief examination of sex-related differences in these mechanisms. Finally, we suggest more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.

show abstract

“…Respiratory propriospinal neurons have been described in the spinal cord of the cat, dog, rat, mouse, and human. They are located in cervical, thoracic and lumbar spinal segments and are distributed throughout the ventral horn, intermediate laminae, and dorsal horn (for reviews, see Lane, 2011;Ikeda et al, 2017;Zaki Ghali et al, 2019). These neurons include pre-phrenic neurons in C3-6 (near the phrenic nucleus, whose motor neurons innervate the diaphragm) as well as high cervical spinal cord neurons in C1-2 (Oku et al, 2008;Okada et al, 2009;Jones et al, 2012).…”

Section: Propriospinal Neurons Shape the Pattern Of Respiratory Motormentioning

confidence: 99%

Role of Propriospinal Neurons in Control of Respiratory Muscles and Recovery of Breathing Following Injury

Jensen

Alilain

Crone

2020

Front. Syst. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Pre-phrenic interneurons: Characterization and role in phrenic pattern formation and respiratory recovery following spinal cord injury

Cited by 27 publications

References 103 publications

Retracted: Midbrain control of breathing and blood pressure: The role of periaqueductal gray matter and mesencephalic collicular neuronal microcircuit oscillators

Retracted: Midbrain control of breathing and blood pressure: The role of periaqueductal gray matter and mesencephalic collicular neuronal microcircuit oscillators

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

Role of Propriospinal Neurons in Control of Respiratory Muscles and Recovery of Breathing Following Injury

Contact Info

Product

Resources

About