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Powell, C.

Publications and source records attributed to Powell, C..

3 recordsLinked to original sources

Characterising the Photoplethysmography Pulse Waveform for Use in Human Neuroscience: The Hybrid Excess and Decay (HED) Model

Photoplethysmography (PPG) offers a widely-used, convenient and non-invasive approach to monitoring basic indices of cardiovascular function such as heart rate and blood oxygenation. However, while the pulse waveform, generated by PPG comprises features that are shaped by physiological and psychological factors, it is frequently overlooked in analyses of such data. We suggest that studies could be enriched by exploiting the possibilities afforded by a systematic analysis of PPG waveforms. To do this we initially require a robust and automated means of characterising it, thereby allowing us to examine variations across individuals and between different physiological and psychological contexts. We present a psychophysiologically-relevant model, the Hybrid Excess and Decay (HED) Model, which characterises pulse wave morphology in terms of three underlying pressure waves and a decay function. We show that these parameters capture PPG data with a high degree of precision and, moreover, are sensitive to specific, physiologically-relevant changes within individuals. We present the theoretical and practical basis for the model and demonstrate its performance when applied to a pharmacological dataset of 105 participants receiving intravenous administrations of the sympathomimetic drug isoproterenol (Isoprenaline). We conclude by discussing the possible value in using the HED model to complement standard measures of PPG outputs.

neuroscience

Accumbens D2-MSN hyperactivity drives behavioral supersensitivity

Antipsychotic-induced behavioral supersensitivity is a problematic consequence of long-term treatment with antipsychotic drugs and is characterized by emergence of refractory symptoms and dyskinesias. The underlying mechanisms are unknown, and no rational approaches exist to prevent or reverse antipsychotic-induced supersensitivity. Here we describe major adaptations impacting populations of striatal medium spiny neurons (MSNs) during the development of behavioral supersensitivity and reveal a prominent role played by D2 receptor expressing MSNs. We show that enhanced D2-MSN activity underlies several symptoms spanning from psychostimulant sensitization, to antipsychotic treatment resistance and drug addiction. Our data warn against severe adverse events following antipsychotic treatment discontinuation and offer insight that may inform therapeutic approaches to overcome antipsychotic-induced supersensitivity.

neuroscience

Microglia Stimulate Zebrafish Brain Repair Via a Specific Inflammatory Cascade

The adult zebrafish brain, unlike mammals, has a remarkable regenerative capacity. Although inflammation inhibits regeneration in mammals, it is necessary for zebrafish brain repair. Microglia are resident brain immune cells that regulate the inflammatory response. To explore the microglial role in repair, we used liposomal clodronate, colony stimulating factor-1 receptor (csf1r) inhibition to ablate microglia and two genetic mutants that lacks microglia during brain injury. We found that microglial ablation inhibited injury-induced neurogenesis and regeneration. Microglial suppression specifically attenuated cell proliferation at the progenitor cell amplification stage of neurogenesis. Notably, the loss of microglia impaired phospho-stat3 (signal transducer and activator of transcription 3) and {beta}-catenin signaling by dynamic regulation of tumor necrosis factor-a after injury, and the ectopic activation of stat3 and {beta}-catenin rescued neurogenesis defects caused by microglial loss. Microglial absence leads to neutrophil accumulation, hindering the resolution of inflammation and macrophages are not sufficient for regeneration. These findings reveal specific roles of microglia and inflammatory signaling during zebrafish telencephalic regeneration that should provide strategies to improve mammalian brain repair.

neuroscience