Neural ensembles in the murine medial prefrontal cortex process distinct information during visual perceptual learning.

BACKGROUND: Perceptual learning refers to an augmentation of an organism's ability to respond to external stimuli, which has been described in most sensory modalities. Visual perceptual learning (VPL) is a manifestation of plasticity in visual information processing that occurs in the adult brain, and can be used to ameliorate the ability of patients with visual defects mainly based on an improvement of detection or discrimination of features in visual tasks. While some brain regions such as the primary visual cortex have been described to participate in VPL, the way more general high-level cognitive brain areas are involved in this process remains unclear. Here, we showed that the medial prefrontal cortex (mPFC) was essential for both the training and maintenance processes of VPL in mouse models. RESULTS: We built a new VPL model in a custom-designed training chamber to enable the utilization of miniScopes when mice freely executed the VPL task. We found that pyramidal neurons in the mPFC participate in both the training process and maintenance of VPL. By recording the calcium activity of mPFC pyramidal neurons while mice freely executed the task, distinct ON and OFF neural ensembles tuned to different behaviors were identified, which might encode different cognitive information. Decoding analysis showed that mouse behaviors could be well predicted using the activity of each ON ensemble. Furthermore, VPL recruited more reward-related components in the mPFC. CONCLUSION: We revealed the neural mechanism underlying vision improvement following VPL and identify distinct ON and OFF neural ensembles in the mPFC that tuned to different information during visual perceptual training. These results uncover an important role of the mPFC in VPL, with more reward-related components being also involved, and pave the way for future clarification of the reward signal coding rules in VPL.

Prelimbic neuron assemblies with delayed activation encode the economic decision-making process in a bandit game.

The medial prefrontal cortex (mPFC) is critical to an animal's value-based decision-making process. However, due to heterogeneity of local mPFC neurons, which neuron group and how it contributes to the alteration of the animal's decision is yet to be explored. And the effect of empty reward in this process is often neglected. Here, we adopted a two-port bandit game paradigm for mice and applied synchronized calcium imaging to the prelimbic area of the mPFC. The results showed that neurons recruited in the bandit game exhibit three distinct firing patterns. Specially, neurons with delayed activation (deA neurons1) carried exclusive information on reward type and changes of choice value. We demonstrated that these deA neurons were essential for the construction of choice-outcome correlation and the trial-to-trial modification of decision. Additionally, we found that in a long-term gambling game, members of the deA neuron assembly were dynamically shifting while maintaining the function, and the importance of empty reward feedbacks were gradually elevated to the same level as reward. Together, these results revealed a vital role for prelimbic deA neurons in the gambling tasks and a new perspective on the encoding of economic decision-making.

Prefrontal Cortex Corticotropin-Releasing Factor Neurons Control Behavioral Style Selection under Challenging Situations.

In response to stressors, individuals adopt different behavioral styles, which are essential for survival and form the basis of differential susceptibility to stress-related disorders. Corticotropin-releasing factor (CRF) and the medial prefrontal cortex (mPFC) have predominantly been studied in behavioral response to stress, while the role of mPFC CRF neurons is poorly understood. Using morphology, electrophysiology, and calcium imaging approaches, we characterized mPFC CRF neurons as a unique subtype of GABAergic inhibitory interneurons that were directly engaged in the tail suspension challenge. Genetic ablation or chemogenetic inhibition of dorsal mPFC (dmPFC) CRF neurons increased immobility under the tail-suspension and forced-swimming challenges and induced social avoidance behavior, whereas activation had the opposite effect on the same measures. Furthermore, increasing CRF neuronal activity promoted durable resilience to repeated social defeat stress. These results uncover a critical role of mPFC CRF interneurons in bidirectionally controlling motivated behavioral style selection under stress.

A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex.

Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.