The Gating Role of Cortical Transfer of Socially Derived Information in Emotion Recognition

Background Introduction

Emotion recognition and the subsequent responses are crucial for survival and maintaining social functions. However, how social information is processed to reliably recognize emotions remains unclear. In this new study, the authors reveal the role of an evolutionarily conserved long-range inhibitory/excitatory brain network in these social cognitive processes. This study provides a detailed analysis of the long-range projection network from the medial prefrontal cortex (mPFC) to the retrosplenial cortex (RSC) to uncover its role in the emotion recognition process.

The importance of these findings lies in the fact that deficiencies in emotion recognition can prevent individuals from providing help or avoiding threats when they see changes in others’ emotions. Furthermore, such social cognitive deficits are common in certain psychiatric and neurodevelopmental disorders (e.g., schizophrenia and autism), profoundly impacting patients’ lives. Large-scale brain networks are involved in these social cognitive abilities, especially those that organize the so-called default mode network (DMN) components of the mammalian social brain. However, how these corticocortical networks regulate the circuit mechanisms of emotion recognition remains unknown.

Source of the Paper

The paper was completed jointly by multiple researchers, including Daniel Dautan, Anna Monai, Federica Maltese, Xiao Chang, and Cinzia Molent, with the first authors Daniel Dautan and Anna Monai and the corresponding author Francesco Papaleo. Their research institutions include the Italian Institute of Technology, the Brain-Inspired Intelligence Science and Technology Institute at Fudan University, and Charite University in Berlin. The paper was published in the 2023 issue of “Nature Neuroscience,” with the DOI: https://doi.org/10.1038/s41593-024-01647-x.

Research Workflow

Experimental Design and Process

The study first revealed the presence of subpopulation projections of somatic inhibitory GABAergic neurons from the medial prefrontal cortex (mPFC) to the retrosplenial cortex (RSC) in mice through anatomical tracing. Whether these projections from mPFC to RSC are involved in emotion recognition was proven using optogenetic manipulations and calcium imaging photometry techniques. Additionally, human functional imaging data suggest that these long-range projections and feedback loops play specific roles in emotion recognition.

1. Anatomical Tracing: By injecting cholera toxin subunit B (CTB-647) retrograde tracer into the mouse RSC, the study confirmed inputs from mPFC and used exogenous viral vectors to label somatic neurons in mPFC in vivo.
2. Viral Injection and Optogenetic Manipulation: Composite adeno-associated virus (AAV-dio-NpHR or AAV-dio-ChR2) was injected into som-cre mice’s mPFC, with LED lights placed in RSC to inhibit or excite som projections from mPFC to RSC.
3. Behavioral Testing: Mice were observed for their recognition and reaction behaviors to conspecifics’ emotional changes during an emotion recognition task.
4. Calcium Imaging Photometry Recording: Used calcium indicator (GCaMP6f) expression technology to record calcium ion signal changes at the terminals of somatic neurons from mPFC to RSC during the emotion recognition process.
5. In Vivo Optogenetic Intervention: Optogenetic tools were used to simulate neuronal activity patterns of normal emotion recognition processes in freely moving mice to verify the effect of the optogenetic manipulation model on emotion recognition.

Main Experimental Findings

1. Anatomical and Functional Confirmation of mPFC to RSC Projections: Retrograde tracing and whole-brain mapping confirmed that about 10% of som neurons in mPFC projected to RSC, primarily distributed in the superficial and deep layers of RSC.
2. Involvement of som Projections from mPFC to RSC in Emotion Recognition: Manipulating these long-range projections showed that inhibiting these projections enhanced mice’s recognition of conspecifics’ emotional changes, while activating them inhibited such recognition behavior.
3. Calcium Imaging Recording Results: During emotion recognition, specific fluctuation patterns of calcium signals at the terminals of somatic neurons from mPFC to RSC were observed during short-term emotional change recognition.
4. Role of Feedback Loops: The feedback loop projection from RSC to mPFC also played an important role in emotion recognition, supported by functional imaging data from mouse models.

Results and Conclusion

1. Functional Differences: The projections of som neurons from mPFC to RSC exhibited a different performance in emotion recognition compared to the overall activity of somatic neurons in the entire mPFC: the overall somatic neuronal activity in mPFC increased during emotion change recognition, while the long-range projections to RSC showed a characteristic reduction.
2. Role of Corticocortical Networks in Emotion Recognition: Overall, the inhibitory network from mPFC-som to RSC significantly affects emotion information processing, and this connection is particularly evident for a negatively correlated active pattern in imaging data, which is notably present in emotion recognition.
3. Clinical and Application Value: The study reveals the potential role of these corticocortical projections and feedback loops in the emotion recognition deficits related to psychiatric disorders, providing new perspectives for treating diseases such as schizophrenia.

Research Highlights

1. Detailed description and verification of long-range inhibitory projections from somatic neurons in mPFC to RSC for the first time, demonstrating their vital role in emotion recognition.
2. Utilized advanced optogenetics and calcium imaging techniques based on mouse models for cross-species validation and combined with human functional imaging data, revealing the core function of corticocortical networks in emotion recognition.
3. Elucidated the role of specific corticocortical circuits, demonstrating their unique function in processing and responding to others’ emotions, which has fundamental significance and clinical implications for understanding evolutionarily conserved social cognitive processes.

Summary

This study provides new perspectives for an in-depth understanding of evolutionarily conserved social cognitive processes. By revealing the crucial role of projections from mPFC-som to RSC in emotion recognition, the research achieves not only a fundamental scientific breakthrough but also proposes new potential targets for improving social cognitive function in clinical treatments. The study emphasizes the importance of maintaining cortical excitatory-inhibitory balance in emotion recognition, providing a solid foundation for further research into human emotion cognition.