Anatomical and electrophysiological characterization of a population of dI6 interneurons in the neonatal mouse spinal cord

Griener, Anna; Zhang, Wei; Kao, Henry S. R.; Haque, Farhia; Gosgnach, Simon

doi:10.1016/j.neuroscience.2017.08.031

Cited by 21 publications

(24 citation statements)

References 42 publications

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“…In the mouse spinal cord, Dmrt3 defines a subset of inhibitory dI6 interneurons located around the central canal in laminae VII and VIII that are primed to contribute to locomotion. Whereas previous studies have evaluated the properties of putative dI6 neurons (Dyck et al, 2012, Griener et al, 2017 or the Dmrt3 gene (Andersson et al, 2012), this study selectively targets the Dmrt3-derived population. Here we investigated the properties of Dmrt3-Cre spinal cord interneurons, their molecular and electrophysiological character and their activity at the microcircuit level.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to the dI6 interneurons, it is clear that at least three genetic subpopulations exist, based on the expression of WT1, Dmrt3 or both (Andersson et al, 2012). Evidence suggests that subtypes outside the WT1/Dmrt3-expressing dI6 cells are likely to exist (Griener et al, 2017), but it remains to be established how many subdivisions of the dI6 population exists. Of note, WT1-expressing dI6 neurons also contribute to locomotor circuit function.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits

et al. 2018

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Neuronal networks within the spinal cord, collectively known as the central pattern generator (CPG), coordinate rhythmic movements underlying locomotion. The transcription factor doublesex and mab-3-related transcription factor 3 (DMRT3) is involved in the differentiation of the dorsal interneuron 6 class of spinal cord interneurons. In horses, a non-sense mutation in the Dmrt3 gene has major effects on gaiting ability, whereas mice lacking the Dmrt3 gene display impaired locomotor activity. Although the Dmrt3 gene is necessary for normal spinal network formation and function in mice, a direct role for Dmrt3-derived neurons in locomotor-related activities has not been demonstrated. Here we present the characteristics of the Dmrt3-derived spinal cord interneurons. Using transgenic mice of both sexes, we characterized interneurons labeled by their expression of Cre driven by the endogenous Dmrt3 promoter. We used molecular, retrograde tracing and electrophysiological techniques to examine the anatomical, morphological, and electrical properties of the Dmrt3-Cre neurons. We demonstrate that inhibitory Dmrt3-Cre neurons receive extensive synaptic inputs, innervate surrounding CPG neurons, intrinsically regulate CPG neuron's electrical activity, and are rhythmically active during fictive locomotion, bursting at frequencies independent to the ventral root output. The present study provides novel insights on the character of spinal Dmrt3-derived neurons, data demonstrating that these neurons participate in locomotor coordination.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits

et al. 2018

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“…The spinal cord predates the pallium, and models of spinal circuits for locomotion routinely implicate a layered organization as being necessary for the flexibility of motor rhythms and patterns (e.g., Danner et al., 2017 , Lafreniere-Roula and McCrea, 2005 ). But evidence that supports layered processing in the spinal cord has been indirect, and results largely from studies of “errors” in stepping called deletions ( Dyck et al., 2012 , Griener et al., 2017 , Rybak et al., 2006 , Zhong et al., 2012 ). Another approach to examine layered processing in the spinal cord has been to quantify the changes in locomotor behavior when whole cardinal classes of genetically defined neurons are silenced or eliminated from spinal motor circuits ( Andersson et al., 2012 , Caldeira et al., 2017 , Crone et al., 2008 , Crone et al., 2009 , Dougherty et al., 2013 , Enjin et al., 2017 , Gosgnach et al., 2006 , Lanuza et al., 2004 , Talpalar et al., 2013 , Zhang et al., 2008 , Zhang et al., 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits

et al. 2018

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SummaryLayering of neural circuits facilitates the separation of neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in the brain, layering is not structurally obvious in the spinal cord. But computational studies of motor behaviors have led to the concept of layered processing in the spinal cord. It has been postulated that spinal V3 interneurons (INs) play multiple roles in locomotion, leading us to investigate whether they form layered microcircuits. Using patch-clamp recordings in combination with holographic glutamate uncaging, we demonstrate focal, layered modules, in which ventromedial V3 INs form synapses with one another and with ventrolateral V3 INs, which in turn form synapses with ipsilateral motoneurons. Motoneurons, in turn, provide recurrent excitatory, glutamatergic input to V3 INs. Thus, ventral V3 interneurons form layered microcircuits that could function to ensure well-timed, spatially specific movements.

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“…Both genes are involved in locomotion patterns; NAV2 was shown to be involved in motor coordination and balance in mice [96], while DBX1 was shown to coordinate left-right locomotor activity [97]. In fact, DBX1 is expressed in the same dI6 interneurons as doublesex and mab-3 related transcription factors (DMRT3) [98], known to affect locomotion pattern in horses [99]. Our findings indicate that showjumping horses are selected for neuromuscular control and coordination, and they might have a well-developed endogenous reward system that triggers them to seek fences to jump.…”

Section: Selection For Cns Reward System and Motoneuronal Control Of mentioning

confidence: 99%

Genomic Divergence in Swedish Warmblood Horses Selected for Equestrian Disciplines

Ablondi

Eriksson

Tetu

et al. 2019

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The equestrian sport horse Swedish Warmblood (SWB) originates from versatile cavalry horses. Most modern SWB breeders have specialized their breeding either towards show jumping or dressage disciplines. The aim of this study was to explore the genomic structure of SWB horses to evaluate the presence of genomic subpopulations, and to search for signatures of selection in subgroups of SWB with high or low breeding values (EBVs) for show jumping. We analyzed high density genotype information from 380 SWB horses born in the period 2010–2011, and used Principal Coordinates Analysis and Discriminant Analysis of Principal Components to detect population stratification. Fixation index and Cross Population Extended Haplotype Homozygosity scores were used to scan the genome for potential signatures of selection. In accordance with current breeding practice, this study highlights the development of two separate breed subpopulations with putative signatures of selection in eleven chromosomes. These regions involve genes with known function in, e.g., mentality, endogenous reward system, development of connective tissues and muscles, motor control, body growth and development. This study shows genetic divergence, due to specialization towards different disciplines in SWB horses. This latter evidence can be of interest for SWB and other horse studbooks encountering specialized breeding.

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Anatomical and electrophysiological characterization of a population of dI6 interneurons in the neonatal mouse spinal cord

Cited by 21 publications

References 42 publications

Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits

Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits

Genomic Divergence in Swedish Warmblood Horses Selected for Equestrian Disciplines

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