Biology subjects

Braun, C.

Publications and source records attributed to Braun, C..

3 recordsLinked to original sources

bioRxiv2018

Mutant Screen Reveals the Piccolo’s Control over Depression and Brain-Gonad Crosstalk

Successful sexual reproduction involves complex, genetically encoded interplay between animal physiology and behavior. The rat provides a highly fecund mammalian model for studying how the brain impacts reproduction. Here, we report a forward genetics screen in rats to identify genes that affect reproduction. A panel of 18 distinct rat strains harboring Sleeping Beauty gene trap mutations were analyzed for the ability to reproduce. As expected, our mutant screen identified genes where reproductive failure was connected to gametogenesis (Btrc, Pan3, Spaca6, Ube2k) and embryogenesis (Alk3, Exoc6b, Slc1a3, Tmx4, Zmynd8). In addition, we identified Ata13 (longevity) and Pclo (neuronal disorders), previously not associated with an inability to conceive. Neurologically, Pclo is known to regulate the size of presynaptic vesicle pools. Here, dominant traits in Pclo mutant rats caused epileptiform activity and affected genes supporting GABAergic synaptic transmission (Gabra6, Gabrg3). Recessive traits in Pclo mutant rats transmitted altered reproductive behavior, as homozygous Pclo mutant rats produced gametes but neither sex would mate with wildtype rats. Pclo mutant rat behavior was linked to endophenotypes signifying compromised brain-gonad crosstalk via disturbed GnRH signaling and allelic markers for major depressive disorder in humans (Grm5, Htr2a, Sorcs3, Negr1, Drd2). Thus, by rat genetics, we identified Pclo as a candidate presynaptic factor required for reproduction. Author SummaryPiccolo gene mutations have previously been identified in human cohorts diagnosed with behavioral syndromes that impact ones emotions, including depression and bipolar disorder. Although studies in human populations implicate changes to Piccolos DNA sequence to enhanced susceptibility for behavioral disorders, studies in mouse models have yet to link Piccolo mutations to altered behavior. Here, by a novel genetics approach, we report Piccolo mutation-dependent effects on reproductive behavior in rats, a finding that may turn out to be relevant to the behavioral effects that are associated with human Piccolo gene mutations. Thus, research aimed at understanding how Piccolo functions to regulate reproduction in rats could prove pivotal in our ability to understand neurological mechanisms that influence human emotions.

genetics↗

bioRxiv2018

Functional dynamics underlying near-threshold perception of facial emotions: a magnetoencephalography investigation.

Conscious perception of emotional valence of faces has been proposed to involve top-down and bottom-up information processing. Yet, the underlying neuronal mechanisms of these two processes and the implementation of their cooperation is still unclear. We hypothesized that the networks activated during the interaction of top-down and bottom-up processes are the key substrates responsible for perception. We assessed the participation of neural networks involved in conscious perception of emotional stimuli near the perceptual threshold using a visual-backward-masking paradigm in 12 healthy individuals using magnetoencephalography. Providing visual stimulation near the perceptual threshold enabled us to compare correctly and incorrectly recognized facial emotions and assess differences in top-down modulation for these stimuli using coherence analysis. We found a fronto-parietal network oscillating in the lower gamma band and exerting top-down control as determined by the causality measure of phase slope index. We demonstrated that correct recognition of facial emotions involved high-beta and low-gamma activity in parietal networks, Incorrect recognition was associated with enhanced coupling in the gamma band between left frontal and right parietal regions. Our results indicate that fronto-parietal control of the perception of emotional face stimuli relies on the right-hemispheric dominance of synchronized gamma band activity.

neuroscience↗

bioRxiv2017

Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo

Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation and in disease remains unknown. Thus, the aim of this study was to determine the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. Prenatal development and postnatal maturation are characterized by a cooperation of active CpG methylation and histone marks at cis-regulatory and genic regions to shape the cardiac myocyte transcriptome. In contrast, pathological gene expression in terminal heart failure is accompanied by changes in active histone marks without major alterations in CpG methylation and repressive chromatin marks. Notably, cis-regulatory regions in cardiac myocytes are significantly enriched for cardiovascular disease-associated variants. This study uncovers distinct layers of epigenetic regulation not only during prenatal development and postnatal maturation but also in diseased human cardiac myocytes.

genomics↗