Neural circuit mechanisms for a mirror-induced self-directed behavior

PROJECT SUMMARY The ability to remember one's own features and monitor the current states is a fundamental for self- recognition. To experimentally demonstrate the visual self-recognition, a mirror-induced visual self-recognition (MSR) test was developed for non-human primates, which requires animals to remember visual features of

their own heads as a reference memory and recognize the current status via a mirror reflection. Human brain imaging and electrophysiological studies have suggested several brain regions potentially important for visual self-recognition. Especially, prefrontal cortex (PFC), posterior parietal cortex (PPC) and hippocampus (HPC)

are currently considered to be crucial for visual self-recognition. However, how neurons, circuits and inter- regional network activity in the brain accomplish this remarkable function remains unknown, due to a limited availability of experimental animal models. Although the ability of MSR was initially reported in only few

species, by modifying the experimental conditions to adjust to their nature, birds, fishes and rhesus macaques were also able to show MSR, suggesting that MSR may present in many more species than previously thought. Our goal is to examine the neural circuit mechanisms for MSR using a mouse model, focusing on

how mice remember visual features of the self and recognize the current status via a mirror reflection. Our recent studies indicate that mice display mark-directed head-grooming to remove ink stains on their heads only when a mirror is visibly available. This mark-directed behavior requires long-term mirror

habituation and social experience in the home cage. Our preliminary study with whole-brain neural activity mapping using immediate early gene expression revealed that both the medial PFC (mPFC) and HPC are activated during MSR in mice, suggesting that these brain regions involved in MSR are preserved across

species. We found that chemogenetic inhibitions of ventral HPC impair MSR. Specifically, a subset of ventral hippocampal CA1 (vCA1) neurons is highly reactivated during exposure to a mirror, but not to other conspecifics, and is crucial for MSR in mice. We refer to these as self-responding neurons. Based on our

preliminary data, previous human studies, and anatomical connections, our central hypothesis is that hippocampal-prefrontal cortical circuits may be crucial for MSR. In particular, we posit the conceptual framework that the visual self-image may be developed and stored in a subset of vCA1 neurons through

social experiences and mirror habituation, while mPFC may facilitate visual self-monitoring for MSR by integrating the visual self-image from vCA1. To test these hypotheses, we will examine i) the roles of vHPC and mPFC neural activity on MSR (Aim 1), ii) the roles of self-responding vCA1 neurons on MSR (Aim 2) and

iii) the roles of vCA1→mPFC pathway on MSR (Aim 3). We believe our proposed study is highly adventurous, because it will provide a first demonstration of the detailed functional map of the hippocampal-prefrontal cortical circuit that controls visual self-recognition.