In cases with assumed diagnosis of frontotemporal lobar degeneration (FTLD) , literatures around early 20^th century had already described the presence of intra neuronal structures with characteristic morphology. However, it has long been difficult to making sense of the neuropathological findings and corresponding clinical phenotypes. Recent refinement of the disease concept and remarkable progresses in molecular genetics and biochemistry revealed multiple genetic causes and the identity of several accumulating proteins. These advances allowed further classification and understandings of clinico‐neuropathological relationship in FTLD. This review describes molecular basis of FTLD and briefly introduce our study regarding FTLD due to C9orf72 repeat expansion. No potential conflicts of interest were disclosed.

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Social and environmental stress is a risk factor for mental illnesses. Therefore, the molecular bases of stress‐induced behavioral changes have been studied using various rodent stress model. Authors examined the molecular changes which are induced in the medial prefrontal cortex (mPFC) by acute and chronic stress and their behavioral consequences. Acute stress activates mesocortical dopaminergic pathway and dopamine D1 receptor located in excitatory neurons in mPFC, which suppressed the induction of social avoidance through. Chronic stress suppressed mesocortical dopaminergic pathway via COX‐1‐PGE₂‐EP1, which induces social avoidance. Additionally, chronic stress activates mPFC microglia via Toll‐like receptor 2 and 4, and activated microglia releases proinflammatory cytokines, namely IL‐1α and TNFα, which induces social avoidance. These results revealed that chronic stress induces neuroinflammation which is derived from microglia, leading to stress‐induced behavioral changes. Authors have no potential conflicts of interest to be disclosed.

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Developmental environment is one of important factors to consider about the cause of mental illness, as well as genome and stress related with onset of illness. To clarify the abnormality of neuronal circuits which underlie on the pathophysiology caused by poor developmental environment, we focus on the influence of social isolation during development on brain development. We investigated electrical activity of neuron in medial prefrontal cortex of mouse socially isolated during development and showed that social isolation lower the excitatory synaptic input and increase the inhibitory synaptic input on specific type of pyramidal cell in layer 5 of medial prefrontal cortex, which result in the lower excitability of the pyramidal cell under the imbalance of excitation / inhibition. In the future, we would focus on the function of the specific pyramidal cell in the whole brain and deeply understand the mechanism of abnormal development of brain by social isolation.

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Human brain is a complex system, characterized by its astonishing dynamical neural networks that operate over a wide range of temporal and spatial scales. Particulally, neural netorks involving frontal cortex have been believed to play crucial roles in humal mental activityies. Despite numerous reports describing aberrant neural network on various types of mental disorders, the exact neurophysiological basis remains unclear. On the other hand, a new discipline called “complex netowrk science” is emerging. The complexity and network approaches to neuroimaging data have been provided cruscial insights to functional neural networks in pathological conditions. Electroencephalogram and magnetoencephalogram (E/MEG) can directly measure brain electric and magnetic fields of the cortex with excellent temporal resolution, thereby yielding insight into temporal dynamics within physiologically relevant frequency ranges. Therefore, it is well suited to measure whole‐brain neural network. In this paper, empirical E/MEG studies of the complexity and network analyses in mental disorders are presented and further discussed their future directions. There are no potential conflicts of interest to disclose.

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Despite many new advances in neuroscience and mental health research, it has been difficult to detect the underlying pathophysiology and the search for novel therapeutic compounds for psychiatric disorders. Regarding the translational research areas in psychiatric disorders, now is the time that we need to reconfirm that there are many differences in “mental” between experimental animals such as mice and humans and reconsider the directions of the research. The U.S. National Institute of Mental Health has proposed a new research framework, Research Domain Criteria (RDoC) , to understanding and treating mental disorders. RDoC integrates multiple levels of information, including genetics, molecules, cells, circuits, behavior, physiology, and self‐reports to consider a range of human behavior from normal to abnormal, rather than being a diagnostic guide with categories . In this review paper, we try to reconsider schizophrenia from the viewpoint of “a neural circuit disease” and introduce two neurophysiological indices, auditory steady‐state responses (ASSR) and non‐REM sleep spindle wave to evaluate neural circuits with impaired functions in schizophrenia. These are translatable neurophysiological indices that bridge animal experiments to clinical research and are expected to be used as one of the common tools that enable pathophysiological analysis and discovery for a new drug for psychiatric disorders.

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