Raphe AMPA receptors and nicotinic acetylcholine receptors mediate ketamine-induced serotonin release in the rat prefrontal cortex.

Several lines of evidence indicate that ketamine has a rapid antidepressant-like effect in rodents and humans, but underlying mechanisms are unclear. In the present study, we investigated the effect of ketamine on serotonin (5-HT) release in the rat prefrontal cortex by in vivo microdialysis. A subcutaneous administration of ketamine (5 and 25 mg/kg) significantly increased the prefrontal 5-HT level in a dose-dependent manner, which was attenuated by local injection of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists into the dorsal raphe nucleus (DRN). Direct stimulation of AMPARs in the DRN significantly increased prefrontal 5-HT level, while intra-DRN injection of ketamine (36.5 nmol) had no effect. Furthermore, intra-DRN injection of an α 4 β 2-nicotinic acetylcholine receptor (nAChR) antagonist, dihydro-β-erythroidine (10 nmol), significantly attenuated the subcutaneous ketamine-induced increase in prefrontal 5-HT levels. These results suggest that AMPARs and α 4 β 2-nAChRs in the DRN play a key role in the ketamine-induced 5-HT release in the prefrontal cortex

Femtosecond X-ray emission study of the spin cross-over dynamics in haem proteins

In haemoglobin (consisting of four globular myoglobin-like subunits), the change from the low-spin (LS) hexacoordinated haem to the high spin (HS) pentacoordinated domed form upon ligand detachment and the reverse process upon ligand binding, represent the transition states that ultimately drive the respiratory function. Visible-ultraviolet light has long been used to mimic the ligand release from the haem by photodissociation, while its recombination was monitored using time-resolved infrared to ultraviolet spectroscopic tools. However, these are neither element- nor spin-sensitive. Here we investigate the transition state in the case of Myoglobin-NO (MbNO) using femtosecond Fe Kalpha and Kbeta non-resonant X-ray emission spectroscopy (XES) at an X-ray free-electron laser upon photolysis of the Fe-NO bond. We find that the photoinduced change from the LS (S = 1/2) MbNO to the HS (S = 2) deoxy-myoglobin (deoxyMb) haem occurs in ca. 800 fs, and that it proceeds via an intermediate (S = 1) spin state. The XES observables also show that upon NO recombination to deoxyMb, the return to the planar MbNO ground state is an electronic relaxation from HS to LS taking place in ca. 30 ps. Thus, the entire ligand dissociation-recombination cycle in MbNO is a spin cross-over followed by a reverse spin cross-over process

Femtosecond time-resolved X-ray absorption spectroscopy of anatase TiO2 nanoparticles using XFEL

光触媒ナノ粒子における光照射後10兆分の1秒での電子の動きをX線自由電子レーザーで観測. 京都大学プレスリリース. 2017-07-06.The charge-carrier dynamics of anatase TiO2 nanoparticles in an aqueous solution were studied by femtosecond time-resolved X-ray absorption spectroscopy using an X-ray free electron laser in combination with a synchronized ultraviolet femtosecond laser (268 nm). Using an arrival time monitor for the X-ray pulses, we obtained a temporal resolution of 170 fs. The transient X-ray absorption spectra revealed an ultrafast Ti K-edge shift and a subsequent growth of a pre-edge structure. The edge shift occurred in ca. 100 fs and is ascribed to reduction of Ti by localization of generated conduction band electrons into shallow traps of self-trapped polarons or deep traps at penta-coordinate Ti sites. Growth of the pre-edge feature and reduction of the above-edge peak intensity occur with similar time constants of 300–400 fs, which we assign to the structural distortion dynamics near the surface

Behavioral characteristics of 5-HT2C receptor knockout mice : Locomotor activity, anxiety-, and fear memory-related behaviors

Pharmacological studies have suggested that the serotonin 5-HT2C receptor is involved in locomotor activity, anxiety, and fear memory. However, the results of locomotor activity and anxiety in 5-HT2C receptor knockout mice have been mixed, and the effects of 5-HT2C receptor knockout on contextual fear memory have not yet been addressed. In the present study, we reconcile these inconsistent results by analyzing behavioral data in detail and by examining the effects of 5-HT2C receptor knockout on contextual fear memory. We demonstrated that the higher locomotor activity in 5-HT2C receptor knockout mice was observed only in the late phase of the test, indicating that the analyses in the previous study using the total locomotor activity would lead to variable results. Moreover, by analyzing mouse behavior in detail, we found that 5-HT2C receptor knockout mice displayed a hesitating attitude by staying in the central area as well as risk assessment behavior in the elevated plusmaze test. However, the time spent in the open arms was longer in 5-HT2C receptor knockout mice than in wildtype littermates when a zero-maze test lacking the central area was used. In the contextual fear conditioning test, 5-HT2C receptor knockout mice showed rapid within-session extinction of fear, but not between-session extinction, compared with wild-type littermates. However, this remains inconclusive because the facilitation of extinction might be confounded with higher locomotor activity in 5-HT2C receptor knockout mice. Taken together, the present results provide reasonable explanations about previous inconsistent findings and partially filled the gaps between pharmacological and genetic findings