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Padawer-Curry, J. A.

Publications and source records attributed to Padawer-Curry, J. A..

2 recordsLinked to original sources

Concurrent optogenetic motor mapping of multiple limbs in awake mice reveals cortical organization of coordinated movements

BackgroundMotor mapping allows for determining the macroscopic organization of motor circuits and corresponding motor movement representations on the cortex. Techniques such as intracortical microstimulation (ICMS) are robust, but can be time consuming and invasive, making them non-ideal for cortex-wide mapping or longitudinal studies. In contrast, optogenetic motor mapping offers a rapid and minimally invasive technique, enabling mapping with high spatiotemporal resolution. However, motor mapping has seen limited use in tracking 3-dimensonal, multi-limb movements in awake animals. This gap has left open questions regarding the underlying organizational principles of motor control of coordinated, ethologically relevant movements involving multiple limbs. ObjectiveOur first objective was to develop Multi-limb Optogenetic Motor Mapping (MOMM) to concurrently map motor movement representations of multiple limbs with high fidelity in awake mice. Having established MOMM, our next objective was determine whether maps of coordinated and ethologically relevant motor output were topographically organized on the cortex. MethodsWe combine optogenetic stimulation with a deep learning driven pose-estimation toolbox, DeepLabCut (DLC), and 3-dimentional triangulation to concurrently map motor movements of multiple limbs in awake mice. ResultsMOMM consistently revealed cortical topographies for all mapped features within and across mice. Many motor maps overlapped and were topographically similar. Several motor movement representations extended beyond cytoarchitecturally defined somatomotor cortex. Finer articulations of the forepaw resided within gross motor movement representations of the forelimb. Moreover, many cortical sites exhibited concurrent limb coactivation when photostimulated, prompting the identification of several cortical regions harboring coordinated and ethologically relevant movements. ConclusionsThe cortex appears to be topographically organized by motor programs, which are responsible for coordinated, multi-limbed, and behavioral-like movements.

neuroscience↗

Psychedelic 5-HT2A receptor agonism: neuronal signatures and altered neurovascular coupling.

Psychedelics hold therapeutic promise for mood disorders due to rapid, sustained results. Human neuroimaging studies have reported dramatic serotonin-2A receptor-(5-HT2AR)-dependent changes in functional brain reorganization that presumably reflect neuromodulation. However, the potent vasoactive effects of serotonin have been overlooked. We found psilocybin-mediated alterations to fMRI-HRFs in humans, suggesting potentially altered NVC. To assess the neuronal, hemodynamic, and neurovascular coupling (NVC) effects of the psychedelic 5-HT2AR agonist, 2,5-Dimethoxy-4-iodoamphetamine (DOI), wide-field optical imaging (WFOI) was used in awake Thy1-jRGECO1a mice during stimulus-evoked and resting-state conditions. While DOI partially altered tasked-based NVC, more pronounced NVC alterations occurred under resting-state conditions and were strongest in association regions. Further, calcium and hemodynamic activity reported different accounts of RSFC changes under DOI. Co-administration of DOI and the 5-HT2AR antagonist, MDL100907, reversed many of these effects. Dissociation between neuronal and hemodynamic signals emphasizes a need to consider neurovascular effects of psychedelics when interpreting blood-oxygenation-dependent neuroimaging measures.

neuroscience↗