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Laranjeira, I.

Publications and source records attributed to Laranjeira, I..

3 recordsLinked to original sources

Serotonin modulates neural dynamics in a subspace orthogonal to the choice space

Serotonin (5-HT) is a central neuromodulator which is implicated in, amongst other functions, cognitive flexibility. 5-HT is released from the dorsal raphe nucleus (DRN) throughout nearly the entire forebrain. Little is known, however, about how serotonin affects downstream populations of neurons and how this modulation might support its cognitive functions. Here, we optogenetically stimulated serotonergic neurons in the DRN while recording large parts of the brain with Neuropixels during quiet wakefulness and performance of a perceptual decision-making task. During quiet wakefulness, 5-HT stimulation induced a rapid switch in internal state, as indicated by dilation of the pupil, suppression of hippocampal sharp wave ripples, and increased exploratory behaviors, such as whisking. To elucidate the brain-wide effect of serotonin release we performed acute Neuropixel recordings in seven target locations, a total of 7,478 neurons were recorded across 17 mice. We found that 5-HT stimulation significantly modulated neural activity in all the recorded brain regions, both during quiet wakefulness and task performance. During task performance, however, we observed no change in behavior when stimulating 5-HT. We found that the 5-HT modulation of high-dimensional neural dynamics is confined to a subspace which is orthogonal relative to the choice axis. These observations describe a possible mechanism for the induction of state-dependent stimulus representations, suggesting a neural basis for neuromodulatory effects on brain-wide circuits to flexible decision-making.

neuroscience↗

Citric Acid water as an alternative to water scheduling in behaving mice

AO_SCPLOWBSTRACTC_SCPLOWPowerful neural measurement and perturbation tools have positioned mice as an ideal species for probing the neural circuit mechanisms of cognition. Crucial to this success is the ability to motivate animals to perform specific behaviors. One successful strategy is to restrict their water intake, rewarding them with water during a behavioral task. However, water restriction requires rigorous monitoring of animals health and hydration status and can be challenging for some mice. We present an alternative that allows mice more control over their water intake: free home-cage access to water, made slightly sour by a small amount of citric acid (CA). In a previous study, rats with free access to CA water readily performed a behavioral task for water rewards, although completing fewer trials than under water restriction (Reinagel, 2018). We here extend this approach to mice and confirm its robustness across multiple laboratories. Mice reduced their intake of CA water while maintaining healthy weights. Continuous home-cage access to CA water only subtly impacted their willingness to perform a decision-making task, in which they were rewarded with sweetened water. When free CA water was used instead of water restriction only on weekends, learning and decision-making behavior were unaffected. CA water is thus a promising alternative to water restriction, allowing animals more control over their water intake without interfering with behavioral performance. SO_SCPLOWIGNIFICANCEC_SCPLOW SO_SCPLOWTATEMENTC_SCPLOWHigh-throughput, reliable behavioral training is a key requirement for the use of mice in behavioral and systems neuroscience, but depends crucially on ability to motivate animals to perform specific behaviors. Here, we present an alternative method to commonly used methods of water restriction: free home-cage access to water, made slightly sour by a small amount of citric acid. This non-labor-intensive, low-error option benefits animal health without hindering behavioral training progress. Citric acid water can serve as a reliable and standardized strategy to achieve high quality task behavior, further facilitating the use of mice in high-throughput behavioral studies.

neuroscience↗

A standardized and reproducible method to measure decision-making in mice

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We designed a task for head-fixed mice that combines established assays of perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be successfully reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path towards achieving reproducibility in neuroscience through collaborative open-science approaches.

neuroscience↗