Search bioRxiv⌕ Search

Biology subjects

Cazettes, F.

Publications and source records attributed to Cazettes, F..

7 recordsLinked to original sources

Neural responses underlying ITD discrimination as a function of sensory reliability in the barn owl

Discrimination of sensory stimuli is fundamentally constrained by the information encoded in neuronal responses. In the barn owl, interaural time difference (ITD) serves as a primary cue for azimuthal sound localization and is represented topographically in the midbrain auditory space map in the external nucleus of the inferior colliculus (ICx). While prior studies have demonstrated a correspondence between spatial tuning and behavioral acuity, it remains unclear how changes in sensory reliability influence this relationship. Here, we examined how behavioral and neuronal ITD discrimination thresholds vary with binaural correlation (BC), which manipulates ITD cue reliability. Using the pupil dilation response (PDR) as a behavioral metric in head-fixed owls, we found that ITD just-noticeable-differences increased exponentially as BC decreased. In contrast, the widths of ICx ITD tuning curves increased more modestly, indicating that tuning resolution alone does not account for behavioral discrimination performance. By computing the Fisher information from ICx neuronal responses, we showed that the average neuronal discriminability predicts behavioral thresholds across BC levels. A habituation-based model incorporating BC-dependent changes in tuning width, firing rate, and response variability successfully accounted for both direction and ITD discrimination. These findings support a model in which perceptual acuity is governed by the combined influence of neuronal tuning and variability and provide a unified framework for understanding how midbrain auditory representations underlie adaptive spatial hearing.

neuroscience↗

Facial expressions in mice reveal latent cognitive variables and their neural correlates

Brain activity controls adaptive behavior but also drives unintentional incidental movements. Such movements could thus potentially be used to read out internal cognitive variables also neurally computed. Establishing this, however, would require ruling out that incidental movements reflect cognition only because they are coupled with task-related responses through the biomechanics of the body. We addressed this issue in a foraging task for mice where multiple decision variables are simultaneously encoded even if, at any given time, only one of them is used. We found that characteristic features of the face simultaneously encode not only the currently used decision variables, but also independent and unexpressed ones, and we show that these features partially originate from neural activity in the secondary motor cortex. Our results suggest that the face reflects ongoing computations above and beyond those related to task demands, demonstrating the ability of noninvasive monitoring to expose otherwise latent cognitive states.

neuroscience↗

Reservoir of decision strategies in the mouse brain

In any given situation, the environment can be parsed in different ways to define useful decision variables (DVs) for any task, but the way in which this manifold of potential decision strategies is processed to shape behavioral policies is not known. We recorded neural ensembles in the frontal cortex of mice performing a foraging task admitting multiple DVs. Methods developed to uncover the currently employed DV revealed the use of multiple strategies and latent changes in strategy within sessions. Optogenetic manipulations showed that the secondary motor cortex (M2) is needed for mice to use the different DVs in the task. Surprisingly, we found that, regardless of the DV best explaining the behavior of each mouse, M2 activity reflected a full basis set of computations spanning a repertoire of DVs extending beyond those useful for the present task. This form of multiplexing may confer considerable advantages for learning and adaptive behavior.

neuroscience↗

Phasic activation of dorsal raphe serotonergic neurons increases pupil-linked arousal

Variations in pupil size under constant luminance are closely coupled to changes in arousal state [1-5]. It is assumed that such fluctuations are primarily controlled by the noradrenergic system [6-9]. Phasic activity of noradrenergic axons precedes pupil dilations associated with rapid changes in arousal [7,9], and is believed to be driven by unexpected uncertainty [1,10-16]. However, the role of other modulatory pathways in the control of pupil-linked arousal has not been as thoroughly investigated, but evidence suggests that noradrenaline may not be alone [7,17,18]. Administration of serotonergic drugs seems to affect pupil size [19-23], but these effects have not been investigated in detail. Here, we show that transient serotonin (5-HT) activation, like noradrenaline, causes pupil-size changes. We used phasic optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DRN) in head-fixed mice locomoting in a foraging task. 5-HT-driven modulations of pupil size were maintained throughout the photostimulation period and sustained for several seconds after the end of the stimulation. The activation of 5-HT neurons increased pupil size additively with locomotor speed, suggesting that 5-HT transients affect pupil-linked arousal independently from locomotor states. We found that the effect of 5-HT on pupil size depended on the level of environmental uncertainty, consistent with the idea that 5-HT may report a salience or surprise signal [24]. Together, these results challenge the classic view of the neuromodulatory control of pupil-linked arousal, revealing a tight relationship between the activation of 5-HT neurons and changes in pupil size.

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↗

Emergence of an adaptive command for orienting behavior in premotor brainstem neurons of barn owls

The midbrain map of auditory space commands sound-orienting responses in barn owls. Owls precisely localize sounds in frontal space but underestimate the direction of peripheral sound sources. This bias for central locations was proposed to be adaptive to the decreased reliability in the periphery of sensory cues used for sound localization by the owl. Understanding the neural pathway supporting this biased behavior provides a means to address how adaptive motor commands are implemented by neurons. Here we find that the sensory input for sound direction is weighted by its reliability in premotor neurons of the owls midbrain tegmentum such that the mean population firing rate approximates the head-orienting behavior. We provide evidence that this coding may emerge through convergence of upstream projections from the midbrain map of auditory space. We further show that manipulating the sensory input yields changes predicted by the convergent network in both premotor neural responses and behavior. This work demonstrates how a topographic sensory representation can be linearly read out to adjust behavioral responses by the reliability of the sensory input.\n\nSignificance statementThis research shows how statistics of the sensory input can be integrated into a behavioral command by readout of a sensory representation. The firing rate of midbrain premotor neurons receiving sensory information from a topographic representation of auditory space is weighted by the reliability of sensory cues. We show that these premotor responses are consistent with a weighted convergence from the topographic sensory representation. This convergence was also tested behaviorally, where manipulation of stimulus properties led to bidirectional changes in sound localization errors. Thus a topographic representation of auditory space is translated into a premotor command for sound localization that is modulated by sensory reliability.

neuroscience↗