Biology subjects

Wang, E. H.-J.

Publications and source records attributed to Wang, E. H.-J..

3 recordsLinked to original sources

bioRxiv2022

Meta-analysis of the autism gut microbiome identifies factors influencing study discrepancies and machine learning classification

Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder and accumulating evidence has suggested that dysbiosis of the gut microbiome plays an essential role. However, a body of research has investigated the ASD gut microbiome without consensus as to whether or how the ASD microbiome differs from neurotypical children. Here, we evaluate the underlying factors leading to study discrepancies by performing a meta-analysis on reprocessed 16S ribosomal RNA gene amplicon (16S) sequencing data. We compile a total of 1,740 samples across 13 carefully selected published studies together with samples from the American Gut Project, and analyze the data in aggregate and from a per-study perspective. We observed increased Bifidobacterium, Actinobacteria, and Prevotella among ASD individuals across cohorts. We further identified associations to Desulfovibrionales, Deltaproteobacteria and Prevotella that were dependent upon which 16S variable regions were sequenced. Utilizing machine learning (ML), we obtained increased accuracy in ASD classification using data collected from certain territories, on younger subjects, on unrelated age-matched rather than related controls, on samples with increased sequencing depth and when accounting for sex differences. Our work provides compelling evidence that the gut microbiome is altered in ASD patients, and highlights novel factors that are important considerations for future studies.

microbiology↗

bioRxiv2020

Divergent pallidal pathways underlying distinct Parkinsonian behavioral deficits

The basal ganglia are a group of subcortical nuclei that regulates motor and cognitive functions1,2. Recent identification of neuronal heterogeneity in the basal ganglia suggests that functionally distinct neural circuits defined by their efferent projections exist even within the same nuclei3-5. This distinction may account for a multitude of symptoms associated with basal ganglia disorders such as Parkinsons disease (PD)6,7. However, our incomplete understanding of the basal ganglia functional organization has hindered further investigation of individual circuits that may underlie different behavioral symptoms in disease states. Here we functionally define two distinct classes of parvalbumin-expressing neurons in the mouse external globus pallidus (GPe-PV) embedded within discrete neural pathways and establish their contributions to different Parkinsonian behavioral deficits. We find that GPe-PV neurons projecting to the substantia nigra pars reticulata (SNr) or parafascicular thalamus (PF) undergo different electrophysiological adaptations in response to dopamine depletion. Furthermore, counteracting these adaptations in each population can selectively alleviate movement deficits or behavioral inflexibility in a Parkinsonian mouse model. Our findings provide a novel framework to understand the circuit basis of separate behavioral symptoms in Parkinsonian state which could provide better strategies for the treatment of PD.

neuroscience↗

bioRxiv2018

Brainstem control of urethral sphincter relaxation and scent marking behavior

Urination may occur either reflexively in response to a full bladder or deliberately irrespective of immediate need. Voluntary control is desired because it ensures that waste is expelled when consciously desired and socially appropriate1,2. Urine release requires two primary components: bladder pressure and urethral relaxation1-3. Although the bladder contracts during urination, its slow smooth muscle is not under direct voluntary control and its contraction alone is not sufficient for voiding. The decisive action of urination is at the urethral sphincter, where striated muscle permits fast control. This sphincter is normally constricted, but relaxes to enable urine flow. Barringtons nucleus (Bar, or pontine micturition center) in the brainstem is known to be essential for the switch from urine storage to elimination4-7, and a subset of Bar neurons expressing corticotropin releasing hormone (BarCRH) have recently been shown to promote bladder contraction8-10. However, Bar neurons that relax the urethral sphincter to enable urination behavior have not been identified. Here we describe novel brainstem neurons that control the external urethral sphincter. We find that scent marking behavior in male mice depends upon a subpopulation of spatially clustered Bar neurons that express high levels of estrogen receptor 1 (BarESR1). These neurons are glutamatergic, project to urinary nuclei in the spinal cord with a bias towards sphincter-inhibiting interneurons, and their activity correlates with natural urination. Optogenetic stimulation of BarESR1 neurons rapidly initiates sphincter bursting and efficient voiding in absence of sensory cues in anesthetized and behaving animals. Conversely, inhibiting the activity of these neurons prevents olfactory cues from promoting scent marking behavior. The identification of BarESR1 cells provides an expanded model for the supraspinal control of urination and its dysfunction.

neuroscience↗