Biology subjects

Mainen, Z.

Publications and source records attributed to Mainen, Z..

6 recordsLinked to original sources

bioRxiv2024

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↗

bioRxiv2022

Maturation of prefrontal input to dorsal raphe increases behavioral persistence in mice

The ability to persist towards a desired objective is a fundamental aspect of behavioral control whose impairment is implicated in several behavioral disorders. One of the prominent features of behavioral persistence is that its maturation occurs relatively late in development. This is presumed to echo the developmental time course of a corresponding circuit within late-maturing parts of the brain, such as the prefrontal cortex, but the specific identity of the responsible circuits is unknown. Here, we describe the maturation of the projection from layer 5 neurons of the prefrontal cortex to the dorsal raphe nucleus in mice. We show using pathway-specific optogenetic stimulation that this connection undergoes a dramatic increase in synaptic potency between postnatal weeks 3 and 8, corresponding to the transition from juvenile to adult. We then show that this period corresponds to an increase in the behavioral persistence that mice exhibit in a foraging task. Finally, we use genetic targeting to selectively ablate this pathway in adulthood and show that mice revert to a behavioral phenotype similar to juveniles. These results suggest that the prefrontal to dorsal raphe pathway is a critical anatomical and functional substrate of the development and manifestation of behavioral control.

neuroscience↗

bioRxiv2021

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↗

bioRxiv2020

Stress-sensitive brain computations of task controllability

Estimating the controllability of the environment enables agents to better predict upcoming events and decide when to engage controlled action selection. How does the human brain estimate controllability? Trial-by-trial analysis of choices, decision times, and neural activity in an explore-and-predict task demonstrate that humans solve this problem by comparing the predictions of an "actor" model with those of a reduced "spectator" model of their environment. Neural BOLD responses within striatal and medial prefrontal areas tracked the instantaneous difference in the prediction errors generated by these two statistical learning models. BOLD activity in the posterior cingulate, temporoparietal, and prefrontal cortices covaried with changes in estimated controllability. Exposure to inescapable stressors biased controllability estimates downward and increased reliance on the spectator model in an anxiety-dependent fashion. Taken together, these findings provide a mechanistic account of controllability inference and its distortion by stress exposure.

neuroscience↗

bioRxiv2020

Metastable attractors explain the variable timing of stable behavioral action sequences

Natural animal behavior displays rich lexical and temporal dynamics, even in a stable environment. The timing of self-initiated actions shows large variability even when they are executed in reliable, well-learned sequences. To elucidate the neural mechanism underlying this mix of reliability and stochasticity, we trained rats to perform a stereotyped sequence of self-initiated actions and recorded neural ensemble activity in secondary motor cortex (M2), known to reflect trial-by-trial action timing fluctuations. Using hidden Markov models, we established a dictionary between ensemble activity patterns and actions. We then showed that metastable attractors, with a reliable sequential structure yet high transition timing variability, could be produced by coupling a high-dimensional recurrent network and a low-dimensional feedforward one. Transitions between attractors in our model were generated by correlated variability arising from the feedback loop between the two networks. This mechanism predicted aligned, low-dimensional noise correlations that were empirically verified in M2 ensembles. Our work establishes a novel framework for investigating the circuit origins of self-initiated behavior based on correlated variability.

neuroscience↗

bioRxiv2020

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↗