Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network structure as well as the identification of CPG neurons. I address the identification of excitatory CPG neurons and their role in rhythm generation, the organization of flexor-extensor networks, and the diverse role of commissural interneurons in coordinating left-right movements. Molecular and genetic approaches that have the potential to elucidate the function of populations of CPG interneurons are also discussed.

Locomotor circuits in the mammalian spinal cord

Recent experiments in vivo and in vitro have advanced our understanding of the sites and mechanisms involved in mammalian respiratory rhythm generation. Here we evaluate and interpret the new evidence for two separate brainstem respiratory oscillators and for the essential role of emergent network properties in rhythm generation. Lesion studies suggest that respiratory cell death might explain morbidity and mortality associated with neurodegenerative disorders and ageing.

/pdf/looking-for-inspiration-new-perspectives-on-respiratory-39nub9tzg7.pdf

Looking for inspiration: new perspectives on respiratory rhythm.

Breathing is an essential behavior that presents a unique opportunity to understand how the nervous system functions normally, how it balances inherent robustness with a highly regulated lability, how it adapts to both rapidly and slowly changing conditions, and how particular dysfunctions result in disease. We focus on recent advancements related to two essential sites for respiratory rhythmogenesis: (a) the preBotzinger Complex (preBotC) as the site for the generation of inspiratory rhythm and (b) the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) as the site for the generation of active expiration.

https://scholarworks.wm.edu/cgi/viewcontent.cgi?article=2713&context=aspubs

Understanding the rhythm of breathing: so near yet so far

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009 A systematic review of this literature found that riluzole had a wide range of effects on factors influencing neural activity in general, and the neuromotor system in particular These effects occurred over a large dose range ( 1 mM) Reported neural effects of riluzole included (in approximate ascending order of dose range): inhibition of persistent Na+ current = inhibition of repetitive firing < potentiation of calcium-dependent K+ current < inhibition of neurotransmitter release < inhibition of fast Na+ current < inhibition of voltage-gated Ca2+ current = promotion of neuronal survival or growth factors < inhibition of voltage-gated K+ current = modulation of two-pore K+ current = modulation of ligand-gated neurotransmitter receptors = potentiation of glutamate transporters Only the first four of these effects commonly occurred at clinically relevant concentrations of riluzole (plasma levels of 1-2 mu M with three- to four-fold higher concentrations in brain tissue) Treatment of human ALS patients or transgenic rodent models of ALS with riluzole most commonly produced a modest but significant extension of lifespan Riluzole treatment was well tolerated in humans and animals In animals, despite in vitro evidence that riluzole may inhibit rhythmic motor behaviors, in vivo administration of riluzole produced relatively minor effects on normal respiration parameters, but inhibited hypoxia-induced gasping This effect may have implications for the management of hypoventilation and sleep-disordered breathing during end-stage ALS in humans

/pdf/a-review-of-the-neural-mechanisms-of-action-and-clinical-203218xbbd.pdf

A Review of the Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating Amyotrophic Lateral Sclerosis: What have we Learned in the Last Decade?

https://www.cell.com/neuron/pdf/S0896-6273(15)00676-5.pdf

Neural Control of Breathing and CO2 Homeostasis

https://www.cell.com/neuron/pdf/S0896-6273(04)00392-7.pdf

Marjorie A Parkis

Papers

Differential Contribution of Pacemaker Properties to the Generation of Respiratory Rhythms during Normoxia and Hypoxia