Biology subjects

Soto, D.

Publications and source records attributed to Soto, D..

23 records · Page 2Linked to original sources

bioRxiv2019

TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Changes in TRESK K+ channel expression/function enhance sensory neurons excitability, but its role in somatosensory perception and nociception is poorly understood. We show that TRESK regulates the sensitivity to mechanical and cold stimuli but not the perception of heat. TRESK knockout mice nociceptive neurons present an enhanced excitability; skin nociceptive C-fibers show an increased activation by lower intensity cold or mechanical stimulation and mice lacking TRESK present mechanical and cold hypersensitivity. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that it regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by low-intensity stimuli.

neuroscience↗

bioRxiv2019

Machine learning predicts human prospective decision making

Metacognition can be deployed retrospectively -to reflect on the correctness of our behavior- or prospectively -to make predictions of success in ones future behavior or make decisions about strategies to solve future problems. We investigated the factors that determine prospective decision making. Human participants performed a visual discrimination task followed by ratings of visibility and response confidence. Prior to each trial, participants made prospective judgments. In Experiment 1, they rated their belief of future success. In Experiment 2, they rated their decision to adopt a focused attention state. Prospective beliefs of success were associated with no performance changes while prospective decisions to engage attention were followed by better self-evaluation of the correctness of behavioral responses. Using standard machine learning classifiers we found that the current prospective decision could be predicted from information concerning task-correctness, stimulus visibility and response confidence from previous trials. In both Experiments, awareness and confidence were more diagnostic of the prospective decision than task correctness. Notably, classifiers trained with prospective beliefs of success in Experiment 1 predicted decisions to engage in Experiment 2 and vice-versa. These results indicate that the formation of these seemingly different prospective decisions share a common, dynamic representational structure.

neuroscience↗

bioRxiv2019

Homomeric Q/R edited AMPA receptors conduct when desensitized

Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors, which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we report the surprising finding that homomeric Q/R edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits ({gamma}-2, {gamma}-8 or GSG1L), generates large steady-state currents and anomalous current-variance relationships. Using fluctuation analysis, single-channel recording, and kinetic modeling we demonstrate that the steady-state current is mediated predominantly by conducting desensitized receptors. When combined with crystallography this unique functional readout of a hith-erto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes within the plasma membrane.

neuroscience↗

bioRxiv2018

Learning multiple concurrent higher-order visual sequences in human primary visual cortex

Learning and memory are supported by a network involving the medial temporal lobe and linked neocortical regions. Emerging evidence indicates that primary visual cortex (i.e., V1) may contribute to recognition memory, but this has been tested only with a single visuospatial sequence as the target memorandum. The present study used functional magnetic resonance imaging to investigate whether human V1 can support the learning of multiple, concurrent, and complex visual sequences involving discontinous (second-order) associations. Two peripheral, goal-irrelevant but structured sequences of orientated gratings appeared simultaneously in fixed locations of the right and left visual fields alongside a central, goal-relevant sequence that was in the focus of spatial attention. Pseudorandom sequences were introduced at multiple intervals during the presentation of the three structured visual sequences to provide an online measure of sequence-specific knowledge at each retinotopic location. We found that a network involving the precuneus and V1 was involved in learning the structured sequence presented at central fixation, whereas right V1 was modulated by repeated exposure to the concurrent structured sequence presented in the left visual field. The same result was not found in left V1. These results indicate for the first time that human V1 can support the learning of multiple concurrent sequences involving complex discontinuous inter-item associations, even peripheral sequences that are goal-irrelevant.

neuroscience↗

bioRxiv2017

How the human brain introspects about one’s own episodes of cognitive control

Metacognition refers to our capacity to reflect upon our experiences, thoughts and actions. Metacognition processes are linked to cognitive control functions that allow keeping our actions on-task. But it is unclear how the human brain builds an internal model of ones cognition and behaviour. We conducted 2 fMRI experiments in which brain activity was recorded online as participants engaged in a memory-guided search task and then later offline when participants introspected about their prior experience and cognitive states during performance. In Experiment 1 the memory cues were task-relevant while in Experiment 2 they were irrelevant. Across Experiments, the patterns of brain activity, including frontoparietal regions, were similar during on-task and introspection states. However the connectivity profile amongst frontoparietal areas was distint during introspection and modulated by the relevance of the memory cues. Introspection was also characterized by increased temporal correlation between the default-mode network (DMN), frontoparietal and dorsal attention networks and visual cortex. We suggest that memories of ones own experience during task performance are encoded in large-scale patterns of brain activity and that coupling between DMN and frontoparietal control networks may be crucial to build an internal model of ones behavioural performance.

neuroscience↗