Our Publications

Chronic social stress is a risk factor for depression. The vulnerability to chronic social stress may be related to changes in social information processing by the hippocampus, a brain region that is crucial for social memory formation. Using a miniature microscope to compare hippocampal activity of mice that are either susceptible or resilient to chronic social stress, we found a poorer hippocampal representation of social information and weaker social memory in susceptible than in resilient mice. Thus, the vulnerability to develop depression may be related to the hippocampal processing of social information.

A crucial component of social memory is the ability to recognize individuals. By pairing negatively and positively valenced experiences with individual social targets, the recognition of mouse identity can be examined in C57BL/6 mice. These paradigms allow for the study of mechanisms of social memory of individual social targets in healthy and disease-related mouse models with impaired social cognition.

Amyloid plaques and neurofibrillary tangles are two pathological hallmarks of Alzhemier’s diseases. The relationship between plaques and tangles on the development of Alzheimer’s disease remains unclear. Using a rat model that expresses plaques and tangles, we found that surprisingly, the early accumulation of phosphorylated tau, a protein that can be found in tangles, rescued neural and cognitive impairment caused by plaques. Although these rescuing effects are transient, further understanding the rescuing effects of phosphorylated tau may reveal mechanisms that could slow down the progression of Alzheimer’s disease.

AMPA receptor is a type of protein in the nervous system that mediates neural communications. In this editorial, we summarized recent papers that published in a research topic on the role of AMPA receptors in brain diseases in Frontiers of Synaptic Neuroscience.

Social experience can be rewarding or aversive. These valence properties could have significant impact on how social information is processed and stored. We proposed that the hippocampus, a brain region that is important for memory formation, is related to the storage of valenced social information. By recording hippocampal activity during social memory formation in male and female mice, we found that the memory of aversive social information in female, but not in male mice, is more generalized. Generalized aversive social memory is related to lower hippocampal activity in female than in male mice. Our findings support a hippocampal mechanism that is related to sex differences in the processing of aversive social information, which could be related to the higher vulnerability to anxiety disorders in women.

AMPA receptor is a protein that can be found on brain cells that mediates neural communications. In this review, we summarized recent findings of the role of AMPA receptors in the regulation of social behaviors in mammals.

Dysbindin-1 is a protein that is reduced in the hippocampus of schizophrenia patients. However, the functional impact of this schizophrenia-related change remains unclear. Using mouse models that allowed us to reduce dysbindin-1 expression in excitatory hippocampal neurons only, we found impaired spatial and social memories and abnormality in neural communications. These findings support the hypothesis that losing dysbindin-1 in hippocampal excitatory neurons contributes to neural and cognitive pathologies that are related to schizophrenia.

Too much dopamine in the brain could mediate cognitive deficits in schizophrenia patients. Nonetheless, which type of receptors for dopamine is responsible for these deficits remain unclear. Using a mouse model of ‘hyperdopaminergia’ by enhancing the levels of dopamine in the hippocampus, we observed impaired spatial and recognition memories. Recognition but not spatial memory deficits was rescued by blocking the D2 dopamine receptors, an action of common antipsychotic drugs. Our evidence supports the therapeutic effect of blocking D2 dopamine receptors on treating some cognitive deficits resulting from the hyperdopaminergia in the hippocampus.

Treatments of major depressive disorder have been related to two neurochemical systems, namely serotonin and glutamate systems. The relationship between these two systems remain unclear. We found that the levels of a small molecular called SNORD90 are elevated in subjects that are responsive to serotonin-targeting antidepressants. In addition, we showed that SNORD90 is responsible for increasing the activity of glutamate system through a protein called neuregulin 3. These findings support a molecular link between monoaminergic antidepressant treatment and glutamatergic neurotransmission.

Our sense of balance and spatial orientation is mediated by the vestibular nucleus. In this study, we revealed the essential and temporal roles of two proteins that mediated neurotransmission, namely NMDA and AMPA receptors, in the development of VN. These findings have important implications on the formation and treatment of development disorders with impairment in balance and spatial orientation.

AMPA receptor is a type of protein in the nervous system that mediates neural communications. In this editorial, we summarized recent papers that published in a research topic on the regulation of the expression and function of AMPA receptors in Frontiers of Synaptic Neuroscience.

The hippocampus is well known for its role in learning and memory. However, recent findings suggest that this brain region mediates our vulnerability to stress-related disorders like depression and anxiety. In this review, we summarized recent findings on the role of the hippocampus in the vulnerability and resistance to stress-related disorders.

Perturbed brain development has been implicated in disorders like schizophrenia. To examine the impact of neural pathway perturbation on brain functions, we tested the effect of ablating excitatory or inhibitory neurons in developing mouse hippocampus, which connects to the frontal lobe of the cerebral cortex called the prefrontal cortex. We found that ablating excitatory, but not inhibitory, hippocampal neurons impaired the activity and neurotransmission in the prefrontal cortex. These effects were mainly observed in a subtype of inhibitory neurons called parvalbumin expressing neurons in the prefrontal cortex. Our results highlight mechanisms that are related to neural circuit pathology in schizophrenia.

NMDA receptors are proteins in the brain that mediate neural communications. Recent findings suggest that NMDA receptors also played important roles in the formation and treatment of stress-related brain disorders like depression. Neural communication occurs primarily in a specialized neural structure called the synapse. Although NMDA receptors can be found inside (synaptic) and outside synapses (extrasynaptic), little is known of the impact of stress on these two populations of NMDA receptors. In this report, we showed that synaptic and extrasynaptic NMDA receptors can be differentially regulated by stress. Our findings have implications for the role of synaptic and extrasynaptic NMDA receptors in the formation and treatment of stress-related brain disorders.

Schizophrenia is increasingly being recognized as a disorder of brain circuits of developmental origin. Animal models, however, have been technically limited in exploring the effects of early developmental circuit abnormalities on the maturation of the brain and associated behavioural outputs. This review discusses evidence of the developmental emergence of circuit abnormalities in schizophrenia, followed by a critical assessment on how animal models need to be adapted through optimized tools in order to spatially and temporally manipulate early developmental events, thereby providing insight into the causal contribution of developmental perturbations to schizophrenia.