Principles of interneuron development learned from Renshaw cells and the motoneuron recurrent inhibitory circuit

Álvarez, Francisco J.; Benito-Gonzalez, Ana; Siembab, Valerie C.

doi:10.1111/nyas.12084

Cited by 41 publications

(38 citation statements)

References 66 publications

(153 reference statements)

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“…In fact, asymmetry with regard to this branch point is not unique to intercostal segments: 3/5 of the cells reported by Lagerbäck and Kellerth (1985a) were without a caudal axonal branch, and Alvarez et al. () noted that the caudal branch of the axon appeared later in development than the rostral branch. Finally, note the differences in diameter in the rostral and caudal branches for the axons illustrated in Figure .…”

Section: Discussionmentioning

confidence: 98%

Axonal projections of Renshaw cells in the thoracic spinal cord

Saywell¹,

Ford

Kirkwood

2013

Physiol Rep

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Renshaw cells are widely distributed in all segments of the spinal cord, but detailed morphological studies of these cells and their axonal branching patterns have only been made for lumbosacral segments. For these, a characteristic distribution of terminals was reported, including extensive collateralization within 1–2 mm of the soma, but then more restricted collaterals given off at intervals from the funicular axon. Previous authors have suggested that the projections close to the soma serve inhibition of motoneurons (known to be greatest for the motor nuclei providing the Renshaw cell excitation) but that the distant projections serve mainly the inhibition of other neurons. However, in thoracic segments, inhibition of motoneurons is known to occur over two to three segments (20–40 mm) from the presumed somatic locations of the Renshaw cells. Here, we report the first detailed morphological study of Renshaw cell axons outside the lumbosacral segments, which investigated whether this different distribution of motoneuron inhibition is reflected in a different pattern of Renshaw cell terminations. Four Renshaw cells in T7 or T8 segments were intracellularly labeled with neurobiotin in anesthetized cats and their axons traced for distances ≥6 mm from the somata. The only morphological difference detected within this distance in comparison with Renshaw cells in the lumbosacral cord was a minimal taper in the funicular axons, where in the lumbosacral cord this is pronounced. Patterns of termination were virtually identical to those in the lumbosacral segments, so we conclude that these patterns are unrelated to the pattern of motoneuronal inhibition.

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Section: Discussionmentioning

confidence: 98%

Axonal projections of Renshaw cells in the thoracic spinal cord

Saywell¹,

Ford

Kirkwood

2013

Physiol Rep

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“…At the spinal and brain stem levels, glycinergic interneurons regulate the generation of action potentials on motoneurons through the presynaptic release of glycine and subsequent GlyR activation [22]. These spinal interneurons also control reciprocal inhibition in reflex circuits producing relaxation of antagonistic muscles during the coordinated contraction of agonist muscles, where Renshaw cells regulate motoneuron excitability by recurrent inhibition through a negative feedback loop [23]. …”

Section: Glycinergic Neurotransmissionmentioning

confidence: 99%

Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses

Burgos

Muñoz

Guzmán

et al. 2015

Pharmacological Research

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It is well accepted that ethanol is able to produce major health and economic problems associated to its abuse. Because of its intoxicating and addictive properties, it is necessary to analyze its effect in the central nervous system. However, we are only now learning about the mechanisms controlling the modification of important membrane proteins such as ligand-activated ion channels by ethanol. Furthermore, only recently are these effects being correlated to behavioral changes. Current studies show that the glycine receptor (GlyR) is a susceptible target for low concentrations of ethanol (5 to 100 mM). GlyRs are relevant for the effects of ethanol because they are found in the spinal cord and brain stem where they primarily express the α1 subunit. More recently, the presence of GlyRs was described in higher regions, such as the hippocampus and nucleus accumbens, with a prevalence of α2/α3 subunits. Here, we review data on the following aspects of ethanol effects on GlyRs: 1) direct interaction of ethanol with amino acids in the extracellular or transmembrane domains, and indirect mechanisms through the activation of signal transduction pathways; 2) analysis of α2 and α3 subunits having different sensitivities to ethanol which allows the identification of structural requirements for ethanol modulation present in the intracellular domain and C-terminal region; 3) Genetically modified knock-in mice for α1 GlyRs that have an impaired interaction with G protein and demonstrate reduced ethanol sensitivity without changes in glycinergic transmission; and 4) GlyRs as potential therapeutic targets.

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“…In mature neurons, the activation of GlyR leads to a fast increase in the passive diffusion of anions, mainly chloride ions, into the neurons, resulting in membrane hyperpolarization and reduction in neuronal excitability (Lester et al, 2004;Miller and Smart, 2010;Zeilhofer et al, 2012). It is well accepted that inhibitory GlyR function is critical for the control of several physiologic processes, namely muscle tone, motor coordination, sensory processing, respiratory rhythms, and pain (Lynch, 2009;Callister and Graham, 2010;Zeilhofer et al, 2012;Alvarez et al, 2013). In addition, the critical role of GlyR inhibition in normal physiology is further highlighted by genetic studies in humans that have linked mutations in GlyR genes with hyperekplexia (Harvey et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors

2016

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Glycine receptors (GlyR) are inhibitory Cys-loop ion channels that contribute to the control of excitability along the central nervous system (CNS). GlyR are found in the spinal cord and brain stem, and more recently they were reported in higher regions of the CNS such as the hippocampus and nucleus accumbens. GlyR are involved in motor coordination, respiratory rhythms, pain transmission, and sensory processing, and they are targets for relevant physiologic and pharmacologic modulators. Several studies with protein crystallography and cryoelectron microscopy have shed light on the residues and mechanisms associated with the activation, blockade, and regulation of pentameric Cys-loop ion channels at the atomic level. Initial studies conducted on the extracellular domain of acetylcholine receptors, ion channels from prokaryote homologs-Erwinia chrysanthemi ligand-gated ion channel (ELIC), Gloeobacter violaceus ligand-gated ion channel (GLIC)-and crystallized eukaryotic receptors made it possible to define the overall structure and topology of the Cys-loop receptors. For example, the determination of pentameric GlyR structures bound to glycine and strychnine have contributed to visualizing the structural changes implicated in the transition between the open and closed states of the Cys-loop receptors. In this review, we summarize how the new information obtained in functional, mutagenesis, and structural studies have contributed to a better understanding of the function and regulation of GlyR.

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Principles of interneuron development learned from Renshaw cells and the motoneuron recurrent inhibitory circuit

Cited by 41 publications

References 66 publications

Axonal projections of Renshaw cells in the thoracic spinal cord

Axonal projections of Renshaw cells in the thoracic spinal cord

Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses

Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors

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