Biology subjects

Martin, I. M.

Publications and source records attributed to Martin, I. M..

3 recordsLinked to original sources

bioRxiv2021

Boosting serotonin increases information gathering by reducing subjective cognitive costs

Serotonin is implicated in the valuation of aversive costs, such as delay or physical effort. However, its role in governing sensitivity to cognitive effort, for example deliberation costs during information gathering, is unclear. We show that week-long treatment with a serotonergic antidepressant enhances a willingness to gather information when trying to maximize reward. Using computational modelling, we show this arises from a diminished sensitivity to subjective deliberation costs during the sampling process. This result is consistent with the notion that serotonin alleviates sensitivity to aversive costs in a domain-general fashion, with implications for its potential contribution to a positive impact on motivational deficits in psychiatric disorders.

neuroscience↗

bioRxiv2021

ATP allosterically stabilizes Integrin-linked kinase for efficient force generation

Focal adhesions link the actomyosin cytoskeleton to the extracellular matrix regulating cell adhesion, shape, and migration. Adhesions are dynamically assembled and disassembled in response to extrinsic and intrinsic forces, but how the essential adhesion component intergrin-linked kinase (ILK) dynamically responds to mechanical force and what role ATP bound to this pseudokinase plays remains elusive. Here, we apply force-probe molecular dynamics simulations of human ILK:-parvin coupled to traction force microscopy to explore ILK mechanotransducing functions. We identify two key saltbridge-forming arginines within the allosteric, ATP-dependent force-propagation network of ILK. Disrupting this network by mutation impedes parvin binding, focal adhesion stabilization, force generation, and thus migration. Under tension, ATP shifts the balance from rupture of the complex to protein unfolding, indicating that ATP increases the force threshold required for focal adhesion disassembly. Our study proposes a new role of ATP as an obligatory binding partner for structural and mechanical integrity of the pseudokinase ILK, ensuring efficient cellular force generation and migration.

biophysics↗

bioRxiv2020

SSRIs modulate asymmetric learning from reward and punishment

Human instrumental learning is driven by a history of outcome success and failure. We demonstrate that week-long treatment with a serotonergic antidepressant modulates a valence-dependent asymmetry in learning from reinforcement. In particular, we show that prolonged boosting of central serotonin reduces reward learning, and enhances punishment learning. This treatment induced learning asymmetry can result in lowered positive and enhanced negative expectations. A consequential effect is more rewarding, and less disappointing, experiences and this may, in part, explain the slow temporal evolution of serotonins well-established antidepressant effects.

neuroscience↗