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Spinal cord interneurons play a crucial role in shaping motor output, but their precise identity and circuit connectivity remain unclear. Focusing on the cardinal class of inhibitory V1 interneurons, we define the diversity of four major V1 subsets according to timing of neurogenesis, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Birthdating delineates two early-born (Renshaw and Pou6f2) and two late-born V1 clades (Foxp2 and Sp8) suggesting sequential neurogenesis gives rise to different V1 clades. Neurogenesis did not correlate with motoneuron targeting. Early-born Renshaw cells and late-born Foxp2-V1 interneurons both tightly coupled to motoneurons, while early-born Pou6f2-V1 and late-born Sp8-V1 interneurons did not. V1-clades also greatly differ in cell numbers and diversity. Lineage labeling of the Foxp2-V1 clade shows it contains over half of all V1 interneurons and provides the largest inhibitory input to motoneuron cell bodies. Foxp2-V1 subgroups differ in neurogenesis and proprioceptive input. Notably, one subgroup defined by Otp expression and located adjacent to the lateral motor column exhibits substantial input from proprioceptors, consistent with some Foxp2-V1 cells at this location forming part of reciprocal inhibitory pathways. This was confirmed with viral tracing methods for ankle flexors and extensors. The results validate the previous V1 clade classification as representing unique interneuron subtypes that differ in circuit placement with Foxp2-V1s forming the more complex subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for the ontogenetic and phylogenetic origins of their diversity. SIGNIFICANCE STATEMENT: Spinal interneuron diversity and circuit organization represents a key challenge to understand the neural control of movement in normal adults and also during motor development and in disease. Inhibitory interneurons are a core element of these spinal circuits, acting on motoneurons either directly or via premotor networks. V1 interneurons comprise the largest group of inhibitory interneurons in the ventral horn and their organization remains unclear. Here we present a comprehensive examination of V1 subtypes according to neurogenesis, placement in spinal motor circuits and motoneuron synaptic targeting. V1 diversity increases during evolution from axial-swimming fishes to limb-based mammalian terrestrial locomotion and this is reflected in the size and heterogeneity of the Foxp2-V1 clade which is closely associated to limb motor pools. We show Foxp2-V1 interneurons establish the densest and more direct inhibitory synaptic input to motoneurons, especially on cell bodies. This is of further importance because deficits on motoneuron cell body inhibitory V1 synapses and on Foxp2-V1 interneurons themselves have recently been shown to be affected at early stages of pathology in motor neurodegenerative diseases like amyotrophic lateral sclerosis.
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BACKGROUND: Childhood obesity is a nutrition-related disease with multiple underlying aetiologies. While genetic factors contribute to obesity, the gut microbiome is also implicated through fermentation of nondigestible polysaccharides to short-chain fatty acids (SCFA), which provide some energy to the host and are postulated to act as signalling molecules to affect expression of gut hormones. OBJECTIVE: To study the cumulative association of causal, regulatory, and tagged single nucleotide polymorphisms (SNPs) within genes involved in SCFA recognition and metabolism with obesity. DESIGN: Study participants were non-Hispanic White (NHW, n = 270) and non-Hispanic Black (NHB, n = 113) children (2-5 years) from the Synergistic Theory and Research on Obesity and Nutrition Group (STRONG) Kids 1 Study. SNP variables were assigned values according to the additive, dominant, or recessive inheritance models. Weighted genetic risk scores (GRS) were constructed by multiplying the reassigned values by independently generated ß-coefficients or by summing the ß-coefficients. Ethnicity-specific SNPs were selected for inclusion in GRS by cohort. RESULTS: GRS were directly associated with body mass index (BMI) z-score. The models explained 3.75%, 12.9%, and 26.7% of the variance for NHW/NHB, NHW, and NHB (ß = 0.89 [CI: 0.43-1.35], P = 0.0002; ß = 0.78 [CI: 0.54-1.03], P < 0.0001; ß = 0.74 [CI: 0.51-0.97], P < 0.0001). CONCLUSION: This analysis supports the cumulative association of several candidate genetic variants selected for their role in SCFA signalling, transport, and metabolism with early-onset obesity. These data strengthen the concept that microbiome influences obesity development through host genes interacting with SCFA.
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Etnicidad/genética , Microbioma Gastrointestinal/genética , Obesidad Infantil/genética , Polimorfismo de Nucleótido Simple/genética , Índice de Masa Corporal , Preescolar , Estudios de Cohortes , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Fenotipo , Riesgo , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Picky eating is prevalent among preschoolers and is associated with risk of both underweight and overweight. Although differences in taste perception may be due to genetic variation, it is unclear whether these variations are related to picky eating behavior. The aim of this study was to investigate the association of 6 single nucleotide polymorphisms (SNPs) in 5 candidate genes related to chemosensory perception with picky eating behavior and adiposity in a cohort of preschool-aged children. METHODS: Parents of 2- to 5-year-old non-Hispanic white preschoolers (n = 153) responded to survey questions on demographics, and information regarding their child's breastfeeding history and picky eating behavior. Height and weight were measured to calculate body mass index (BMI) z-scores using standard growth charts, and saliva was collected for genotyping. Generalized linear models were used to examine associations between picky eating behavior and BMI z-scores with genetic variation. RESULTS: When controlling for child age, sex, breastfed status, and parent education level, SNPs in TAS2R38 (rs713598) and CA6 (rs2274327) were associated with picky eating behavior in children. There was no association between SNPs and BMI z-scores. CONCLUSION: Genes related to chemosensory perception may play a role in children's picky eating behavior.
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Anhidrasas Carbónicas/genética , Conducta Alimentaria , Percepción Olfatoria/genética , Receptores Acoplados a Proteínas G/genética , Percepción del Gusto/genética , Conducta Infantil , Preescolar , Femenino , Preferencias Alimentarias , Humanos , Masculino , Nutrigenómica , Polimorfismo de Nucleótido SimpleRESUMEN
Breath sampling and analysis provide healthcare professionals with a practical, noninvasive diagnostic measurement for children with a variety of gastrointestinal (GI) disorders. New biomarkers found in human breath have been investigated and provide the opportunity to diagnose bacterial overgrowth and other underlying causes of GI dysfunction. Although several protocols have been described previously regarding breath sampling, few have demonstrated the feasibility of collection in young children. This communication introduces a simple game that allows for 3- to 7-year-old children to practice breath exhalation to give a proper breath sample in a relaxed and comfortable environment. The technique described offers clinicians a creative approach for obtaining breath samples from a child by reducing the apprehension and anxiety associated with the research and clinical environment.