Humans and animals can sense and respond to aversive experiences of others, an ability crucial for empathy, social bonding and important for survival. Here we study how neural circuits in the brain produce observational fear, a behavior of one subject displaying fearful responses to the observation of another subject in fear. Previous behavioral and human imaging studies have revealed a powerful influence of prior aversive experience on this behavior and have also identified several brain areas involved. However, what neuronal activity patterns in vivo allow one subject to subjectively perceive the others? experiences as aversive remains mysterious. Given the strong influence of prior experience on observational fear, we propose a hypothesis that the subjective sense of fear upon observation is represented by neurons in the anterior cingulate cortex (ACC), but strongly influenced by a particular neuronal activity pattern in the hippocampus (HP), called awake replay, that recalls prior fearful experiences. We will test the hypothesis by simultaneous recording of a large number of single neurons in ACC and HP in rats during observational fear tasks. We will first determine how HP awake replay and the associated ACC activity patterns are correlated with behavioral measures of observational fear and how they are generated within the HP and ACC neural circuits. Second, we will determine how key factors related to prior experience modulate the ACC/HP activity patterns underlying observational fear. In particular, we will study the effects of recency, valence, spatial and social contexts of prior experience. Finally, we will determine how the ACC/HP activity patterns are causally related to observational fear by disrupting these patterns and then examining its impacts on behavioral measures. The outcomes of this study will significantly advance our understanding of neural circuit computations in observational fear and may reveal a specific in vivo neural mechanism of how it can be produced by recalling prior fearful experiences. This study may open the door to understand antisocial symptoms in mental disorders such as antisocial personality disorder and schizophrenia and may inspire novel therapeutic strategies. 1

Public Health Relevance

We propose to study how neural circuits in the brain generate observational fear, a behavior that is related to our ability to feel the pain and suffering experienced by others and is impaired in antisocial personality disorder and other mental disorders. The outcome of this study will significantly improve our understanding of observational fear and may generate new therapeutic strategies for treating antisocial symptoms. 1

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1)
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Vicentic, Aleksandra
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Baylor College of Medicine
Anatomy/Cell Biology
Schools of Medicine
United States
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Mou, Xiang; Cheng, Jingheng; Yu, Yan S W et al. (2018) Comparing Mouse and Rat Hippocampal Place Cell Activities and Firing Sequences in the Same Environments. Front Cell Neurosci 12:332