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This study examined the effect of the acute and repeated per os (p.o.) administration of the selective 5-HT6 receptor antagonist SB-271046, on the number, as well as the firing pattern of spontaneously active dopamine (DA) neurons in the rat substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized male Sprague-Dawley rats. This was accomplished using the technique of extracellular in vivo electrophysiology. A single p.o. administration of either 1, 3, or 10 mg/kg of SB-271046 did not significantly alter the number of spontaneously active SNC DA neurons per stereotaxic electrode tract compared to vehicle-treated animals. The acute administration of either 1 or 3 mg/kg of SB-271046 did not significantly alter the number of spontaneously active VTA DA neurons. In contrast, a significant decrease in the number of spontaneously active VTA DA neurons was observed after a single administration of 10 mg/kg of SB-271046 compared to vehicle-treated animals. The acute p.o. administration of SB-271046 significantly altered the firing pattern parameters of all (bursting + nonbursting DA neurons) DA neurons, particularly those in the VTA, compared to vehicle-treated animals. The repeated p.o. administration (once per day for 21 days) of 1, 3, or 10 mg/kg of SB-271046 did not significantly alter the number of spontaneously active VTA DA neurons compared to vehicle-treated animals. The repeated administration of 3 or 10 mg/kg of SB-271046 significantly increased the number of spontaneously active SNC DA neurons compared to vehicle controls. Overall, the repeated administration of SB-271046 had relatively little effect on the firing pattern of midbrain DA neurons. The results obtained following the chronic administration of SB-271046 show that this compound has a profile different from that of typical or atypical antipsychotic drugs in this model. Clinical studies are required to understand what role 5-HT6 receptor blockade might eventually play in the treatment of schizophrenia. Synapse 52:20–28, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This study examined the effect of the p.o. administration of the putative atypical antipsychotic drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)-6H-[1]benzothieno[2,3b][1,5] benzodiazepine maleate) on the activity of spontaneously active dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) in anesthetized male Sprague-Dawley rats. This was accomplished using in vivo electrophysiology. The acute p.o. administration of Y-931 did not significantly alter the number of spontaneously active SNC DA neurons compared to vehicle-treated animals. A single p.o. administration of 3 and 10 mg/kg of Y-931 significantly increased and decreased, respectively, the number of spontaneously active VTA DA neurons compared to vehicle-treated animals. The acute administration of 3 mg/kg of Y-931 significantly altered the firing pattern parameters for all spontaneously active SNC DA. The 3 and 10 mg/kg doses of Y-931 significantly increased the degree of bursting and irregular activity of spontaneously active VTA and SNC DA neurons firing in a bursting pattern. The repeated p.o. administration (21 days) of 1, 3, or 10 mg/kg of Y-931 significantly decreased the number of spontaneously active VTA DA neurons but had no significant effect on SNC DA neurons compared to vehicle-treated animals. The repeated administration of Y-931 did not significantly alter the firing pattern of all spontaneously active SNC or VTA DA neurons. Our findings indicate that the acute and chronic administration of Y-931 significantly alters the activity of midbrain DA neurons in rats and the electrophysiological profile of chronic Y-931 resembles that of atypical antipsychotic agents. Synapse 51:19–26, 2004. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In this study, we examined the effect of the acute and chronic administration of WAY-405, a selective 5-HT1A receptor antagonist, on the number and firing pattern of spontaneously active substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine (DA) neurons in anesthetized rats. This was accomplished using in vivo, extracellular single unit recording. The i.v. administration of WAY-405 (5–640 μg/kg) did not significantly alter the basal firing rate or pattern of spontaneously active A9 and A10 DA neurons. A single injection of 10 μg/kg of WAY-405 decreased the number of spontaneously active A10 DA neurons and the 100 μg/kg dose significantly decreased the number of spontaneously active A9 and A10 DA neurons compared to vehicle-treated animals. A single injection of 1, 10, or 100 μg/kg of WAY-405 significantly decreased the degree of bursting of A10 DA neurons. In contrast, 1 μg/kg i.p. of WAY-405 significantly increased the percent of A9 DA neurons exhibiting a bursting pattern. The repeated administration of 10 or 100 μg/kg i.p. of WAY-405 (21 days) significantly decreased the number of spontaneously active DA neurons in both the A9 and A10 compared to vehicle-treated animals and this decrease was not reversed by i.v. (+)-apomorphine. The repeated administration of WAY-405 significantly altered the firing pattern of DA neurons, particularly those in the A10 area. Overall, these results indicate that the antagonism of the 5-HT1A receptor significantly alters the activity of midbrain DA neurons in anesthetized rats. Synapse 50:181–190, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We examined energy metabolism and amino acid content in the hippocampus of amygdaloid-kindled rats using1H NMR spectroscopy. Three weeks after the last stage 5 seizure, kindled rats were killed by microwave irradiation. The hippocampus was dissected out and subjected to MeOH/CHCl3 extraction. All1H spectra were analyzed to quantify absolute concentrations using a non-linear least squares method, combined with a prior knowledge of chemical shifts. Saturation effects were compensated for by the T1 measurement of each component. Levels of energy metabolism-related compounds, phosphocreatine, creatine, glucose and succinate were the same in both kindled rats and sham controls. Lactate concentration had a tendency to increase, although this was not statistically significant. When compared with sham controls, levels of aspartate, glutamate, glycine and glutamine, as well as GABA and inositol, were increased in the ipsilateral but not the contralateral hippocampus. In contrast, levels of taurine, alanine and threonine were unchanged. Finally,N-acetylaspartylglutamate content was elevated, whereasN-acetyl-l-aspartate content was unaltered in the ipsilateral hippocampus of kindled animals. Our results suggest that amygdala kindling may affects amino acid metabolism, but not energy metabolism. [ABSTRACT FROM AUTHOR]

Autism is hypothesized to result in a cortical excitatory and inhibitory imbalance driven by inhibitory interneuron dysfunction, which is associated with the generation of gamma oscillations. On the other hand, impaired motor control has been widely reported in autism. However, no study has focused on the gamma oscillations during motor control in autism. In the present study, we investigated the motor-related gamma oscillations in autism using magnetoencephalography. Magnetoencephalographic signals were recorded from 14 right-handed human children with autism (5 female), aged 5-7 years, and age- and IQ-matched 15 typically developing children during a motor task using their right index finger. Consistent with previous studies, the autism group showed a significantly longer button response time and reduced amplitude of motor-evoked magnetic fields. We observed that the autism group exhibited a low peak frequency of motor-related gamma oscillations from the contralateral primary motor cortex, and these were associated with the severity of autism symptoms. The autism group showed a reduced power of motor-related gamma oscillations in the bilateral primary motor cortex. A linear discriminant analysis using the button response time and gamma oscillations showed a high classification performance (86.2% accuracy). The alterations of the gamma oscillations in autism might reflect the cortical excitatory and inhibitory imbalance. Our findings provide an important due into the behavioral and neurophysiological alterations in autism and a potential biomarker for autism. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess cortical hemodynamic response patterns in 3- to 7-year-old children listening to two speech modes: normally vocalized and whispered speech. Understanding whispered speech requires processing of the relatively weak, noisy signal, as well as the cognitive ability to understand the speaker's reason for whispering. Method: Near-infrared spectroscopy (NIRS) was used to assess changes in cortical oxygenated hemoglobin from 16 typically developing children. Results: A profound difference in oxygenated hemoglobin levels between the speech modes was found over left ventral sensorimotor cortex. In particular, over areas that represent speech articulatory body parts and motion, such as the larynx, lips, and jaw, oxygenated hemoglobin was higher for whisper than for normal speech. The weaker stimulus, in terms of sound energy, thus induced the more profound hemodynamic response. This, moreover, occurred over areas involved in speech articulation, even though the children did not overtly articulate speech during measurements. Conclusion: Because whisper is a special form of communication not often used in daily life, we suggest that the hemodynamic response difference over left ventral sensorimotor cortex resulted from inner (covert) practice or imagination of the different articulatory actions necessary to produce whisper as opposed to normal speech. [ABSTRACT FROM AUTHOR]

Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results. TJ- 54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: -0.23 ± 0.08; placebo: -0.03 ± 0.08, P < 0.018), tension (TJ-54: -0.42 ± 0.09; placebo: -0.18 ±0.09, P < 0.045), and poor impulse control (TJ-54: -0.39 ±0.10; placebo: -0.07 ± 0.10, P < 0.037). Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores. [ABSTRACT FROM AUTHOR]

Objective: In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects. Method: KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys. Results: By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys. Conclusions: These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG device has facilitated the acquisition of bi-hemispheric recordings, even in young children. Using the child-customised MEG device, we previously reported that language-related performance was reflected in the strength of the early component (P50m) of the auditory evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5 years old) [Eur J Neurosci 2012, 35:644-650]. The aim of this study was to investigate how this neurophysiological index in each hemisphere is correlated with language performance in autism spectrum disorder (ASD) and TD children. Methods We used magnetoencephalography (MEG) to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. We investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33 young children (3 to 7 years old) with ASD and in 30 young children who were typically developing (TD). The children were matched according to their age (in months) and gender. Most of the children with ASD were highfunctioning subjects. Results The results showed that the children with ASD exhibited significantly less leftward lateralisation in their P50m intensity compared with the TD children. Furthermore, the results of a multiple regression analysis indicated that a shorter P50m latency in both hemispheres was specifically correlated with higher language-related performance in the TD children, whereas this latency was not correlated with non-verbal cognitive performance or chronological age. The children with ASD did not show any correlation between P50m latency and language-related performance; instead, increasing chronological age was a significant predictor of shorter P50m latency in the right hemisphere. Conclusions Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development. [ABSTRACT FROM AUTHOR]