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Biology subjects

Schilling, L.

Publications and source records attributed to Schilling, L..

3 recordsLinked to original sources

Striatal dopamine reflects individual long-term learning trajectories

Learning from naive to expert occurs over long periods of time, accompanied by changes in the brains neuronal signals. The principles governing behavioural and neuronal dynamics during long-term learning remain unknown. We developed a psychophysical visual decision task for mice that allowed for studying learning trajectories from naive to expert. Mice adopted sequences of strategies that became more stimulus-dependent over time, showing substantial diversity in the strategies they transitioned through and settled on. Remarkably, these transitions were systematic; the initial strategy of naive mice predicted their strategy several weeks later. Longitudinal imaging of dopamine release in dorsal striatum demonstrated that dopamine signals evolved over learning, reflecting stimulus-choice associations linked to each individuals strategy. A deep neural network model trained on the task with reinforcement learning captured behavioural and dopamine trajectories. The models learning dynamics accounted for the mices diverse and systematic learning trajectories through a hierarchy of saddle points. The model used prediction errors mirroring recorded dopamine signals to update its parameters, offering a concrete account of striatal dopamines role in long-term learning. Our results demonstrate that long-term learning is governed by diverse yet systematic transitions through behavioural strategies, and that dopamine signals exhibit key characteristics to support this learning.

neuroscience↗

Altered structural connectivity and functional brain dynamics in individuals with heavy alcohol use

Heavy alcohol use and its associated conditions, such as alcohol use disorder (AUD), impact millions of individuals worldwide. While our understanding of the neurobiological correlates of AUD has evolved substantially, we still lack models incorporating whole-brain neuroanatomical, functional, and pharmacological information under one framework. Here, we utilize diffusion and functional magnetic resonance imaging to investigate alterations to brain dynamics in N = 130 individuals with a high amount of current alcohol use. We compared these alcohol using individuals to N = 308 individuals with minimal use of any substances. We find that individuals with heavy alcohol use had less dynamic and complex brain activity, and through leveraging network control theory, had increased control energy to complete transitions between activation states. Further, using separately acquired positron emission tomography (PET) data, we deploy an in silico evaluation demonstrating that decreased D2 receptor levels, as found previously in individuals with AUD, may relate to our observed findings. This work demonstrates that whole-brain, multimodal imaging information can be combined under a network control framework to identify and evaluate neurobiological correlates and mechanisms of AUD.

neuroscience↗

A conserved enzyme of smut fungi facilitates cell-to-cell movement in the plant bundle sheath

The smut fungi are one of the largest groups of fungal plant pathogens, causing disease in all cereal crops. They directly penetrate their hosts and establish a biotrophic interaction. During colonization of the plant, smut fungi secrete a wide range of effector proteins, which suppress plant immunity and modulate cellular functions as well as development of the host, thereby determining the pathogens life-style and virulence potential. The conserved effector Erc1 (enzyme required for cell-to-cell movement) contributes to virulence of the corn smut Ustilago maydis in maize leaves, but not on the tassel. Erc1 binds to host cell wall components and has a 1,3-{beta}-glucanase activity, which is required to attenuate {beta}-glucan-induced defense responses in host leaves. Confocal microscopy revealed that Erc1 has a cell type-specific virulence function, being necessary for fungal cell-to-cell movement in the plant bundle sheath. This cell type-specific virulence function of Erc1 is fully conserved in the barley pathogen Ustilago hordei, which has a functionally conserved Erc1 orthologue. Thus, Erc1 is an enzymatically active core virulence factor with a cell type-specific virulence function in different hosts, which is important for cell-to-cell movement during host colonization of pathogenic smut fungi.

plant biology↗