Biology subjects

Ioanas, H.-I.

Publications and source records attributed to Ioanas, H.-I..

4 recordsLinked to original sources

bioRxiv2020

Whole-Brain Longitudinal Profiling of Serotonergic Reuptake Inhibition

The serotonergic system is widely implicated in affect regulation, and a common target for psychopharmacological interventions. Selective Serotonin Reuptake Inhibitors (SSRIs) are the foremost drug class for treating depression, as well as anxiety, phobia and other affective disorders. However, the functional mechanisms determining SSRI efficacy remain elusive, hindering the targeted further development of serotonergic system interventions. Assays for longitudinal whole-brain interrogation of the serotonergic system are unavailable, yet such techniques are essential for identifying differential intervention effects across projection areas. We present a novel longitudinal opto-fMRI assay suitable for imaging longitudinal drug treatment effects on the mouse serotonergic system -- within-subject and with sub-millimetre spatial resolution. We apply this assay to a longitudinal fluoxetine treatment, and document reliable segmentation of brain-wide treatment effects, including identification of a brainstem cluster with a highly significant longitudinal trajectory, constituting a novel neurophenotype for psychopharmacological interventions. We differentiate serotonergic neuron activation from projection area activation, and offer brain-wide fMRI evidence for the prominent autoinhibition down-regulation theory of SSRI effects. Further, we show that given the sensitivity of the assay, SSRI treatment produces no persistent effects after treatment cessation in healthy subjects.

neuroscience↗

bioRxiv2020

A Whole-Brain Map and Assay Parameter Analysis of Mouse VTA Dopaminergic Activation

Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signalling in the mouse brain is crucial for the translational investigation of motivational control as well as of neuronal function phenotypes for diseases and interventions. In this article we use optogenetic stimulation directed at VTA dopaminergic neurons in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present a comprehensive assay producing the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with its structural VTA projections, diverging only in a few key aspects. While the activation map predominantly highlights target areas according to their relative projection densities (e.g. strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail the variability of the assay with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide evidence-based recommendations for assay reuse, publishing both reference results and a reference analysis workflow implementation.

neuroscience↗

bioRxiv2019

An Automated Open-Source Workflow for Standards-Compliant Integration of Small Animal Magnetic Resonance Imaging Data

Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons. In small animal magnetic resonance imaging, an overwhelming proportion of data is acquired via the ParaVision software of the Bruker Corporation. The original data structure is predominantly transparent, but fundamentally incompatible with modern pipelines. Additionally, it sources metadata from free-field operator input, which diverges strongly between laboratories and researchers. In this article we present an open-source workflow which automatically converts and reposits data from the ParaVision structure into the widely supported and openly documented Brain Imaging Data Structure (BIDS). Complementing this workflow we also present operator guidelines for appropriate ParaVision data input, and a programmatic walk-through detailing how preexisting scans with uninterpretable metadata records can easily be made compliant after the acquisition.

neuroscience↗

bioRxiv2019

An Optimized Registration Workflow and Standard Geometric Space for Small Animal Brain Imaging

The reliability of scientific results critically depends on reproducible and transparent data processing. Cross-subject and cross-study comparability of imaging data in general, and magnetic resonance imaging (MRI) data in particular, is contingent on the quality of registration to a standard reference space. In small animal MRI this is not adequately provided by currently used processing workflows, which utilize high-level scripts optimized for human data, and adapt animal data to fit the scripts, rather than vice-versa. In this fully reproducible article we showcase a generic workflow optimized for the mouse brain, alongside a standard reference space suited to harmonize data between analysis and operation. We introduce four separate metrics for automated quality control (QC), and a visualization method to aid operator inspection. Benchmarking this workflow against common legacy practices reveals that it performs more consistently, better preserves variance across subjects while minimizing variance across sessions, and improves both volume and smoothness conservation RMSE approximately 2-fold. We propose this open source workflow and the QC metrics as a new standard for small animal MRI registration, ensuring workflow robustness, data comparability, and region assignment validity, all of which are indispensable prerequisites for the comparability of scientific results across experiments and centers.

neuroscience↗