Near-infrared spectroscopy (NIRS) is a noninvasive technique for continuous monitoring of the amounts of total hemoglobin (total-Hb), oxygenated hemoglobin, (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb). The purpose of the present study was to demonstrate the utility of NIRS in functional imaging of the human visual cortex. A new NIRS imaging system enabled measurements from 24 scalp locations covering a 9 cm sq area. Topographic images were obtained from interpolations of the concentration changes between measurement points. Five healthy subjects between 25 and 49 years of age were investigated. After a resting baseline period of 50 s, the subjects were exposed to a visual stimulus for 20 s, followed by a 50 s resting period in a dimly lit, sound attenuating room. The visual stimulus was a circular, black and white, alternating checkerboard. In four of five subjects the visual cortex was the most activated area during visual stimulation. This is the first reported use of a NIRS-imaging system for assessing hemodynamic changes in the human visual cortex. The typical hemodynamic changes expected were observed; the total-Hb and oxy-Hb increased just after the start of stimulation and plateaued after 10 s of the stimulation period.

In an in vivo dialysis experiment, the intra-medial frontal cortex infusion of a system A and Asc-1 transporter inhibitor, S-methyl-L-cysteine, caused a concentration-dependent increase in the dialysate contents of an endogenous coagonist for the N-methyl-D-aspartate (NMDA) type glutamate receptor, D-serine, in the cortical portion. These results suggest that these neutral amino acid transporters could control the extracellular D-serine signaling in the brain and be a target for the development of a novel threapy for neuropsychiatric disorders with an NMDA receptor dysfunction.

The Ihara epileptic rat (IER) is a mutant model with limbic-like seizures whose pathology and causative gene remain elusive. In this report, via linkage analysis, we identified Down syndrome cell adhesion molecule-like 1(Dscaml1) as the responsible gene for IER. A single base mutation in Dscaml1 causes abnormal splicing, leading to lack of DSCAML1. IERs have enhanced seizure susceptibility and accelerated kindling establishment. Furthermore, GABAergic neurons are severely reduced in the entorhinal cortex (ECx) of these animals. Voltage-sensitive dye imaging that directly presents the excitation status of brain slices revealed abnormally persistent excitability in IER ECx. This suggests that reduced GABAergic neurons may cause weak sustained entorhinal cortex activations, leading to natural kindling via the perforant path that could cause dentate gyrus hypertrophy and epileptogenesis. Furthermore, we identified a single nucleotide substitution in a human epilepsy that would result in one amino acid change in DSCAML1 (A2105T mutation). The mutant DSCAML1A2105T protein is not presented on the cell surface, losing its homophilic cell adhesion ability. We generated knock-in mice (Dscaml1A2105T) carrying the corresponding mutation and observed reduced GABAergic neurons in the ECx as well as spike-and-wave electrocorticogram. We conclude that DSCAML1 is required for GABAergic neuron placement in the ECx and suppression of seizure susceptibility in rodents. Our findings suggest that mutations in DSCAML1 may affect seizure susceptibility in humans.

The molecular mechanisms underlying neurodevelopmental disorders (NDDs) remain unclear. We previously identified Down syndrome cell adhesion molecule like 1 (Dscaml1) as a responsible gene for Ihara epileptic rat (IER), a rat model for human NDDs with epilepsy. However, the relationship between NDDs and DSCAML1 in humans is still elusive. In this study, we screened databases of autism spectrum disorders (ASD), intellectual disability (ID)/developmental disorders (DD) and schizophrenia for genomic mutations in human DSCAML1. We then performed in silico analyses to estimate the potential damage to the mutated DSCAML1 proteins and chose three representative mutations (DSCAML1C729R, DSCAML1R1685* and DSCAML1K2108Nfs*37), which lacked a cysteine residue in the seventh Ig domain, the intracellular region and the C‐terminal PDZ‐binding motif, respectively. In overexpression experiments in a cell line, DSCAML1C729R lost its mature N‐glycosylation, whereas DSCAML1K2108Nfs*37 was abnormally degraded via proteasome‐dependent protein degradation. Furthermore, in primary hippocampal neurons, the ability of the wild‐type DSCAML1 to regulate the number of synapses was lost with all mutant proteins. These results provide insight into understanding the roles of the domains in the DSCAML1 protein and further suggest that these mutations cause functional changes, albeit through different mechanisms, that likely affect the pathophysiology of NDDs.

We investigated the relationship between hemodynamic changes in the cortex measured by near-infrared spectroscopy (NIRS) and the polysomnographic changes during sleep. Four healthy male volunteers participated in the study. Near-infrared spectroscopy measuring and polysomnographic recordings were done simultaneously during sleep. In many case, oxy-hemoglobin (oxy-Hb) decreased and deoxy-hemoglobin (deoxy-Hb) increased during the transition from wakehlness to sleep, and oxy-Hb increased toward deep sleep. Oxy-Hb and deoxyHb had larger fluctuations during REM sleep than those during non-REM sleep. During REM sleep, oxy-Hb often showed a lower level and deoxy-Hb showed a higher level than those during the preceding and following non-REM sleep.