[Show abstract][Hide abstract] ABSTRACT: Bisphenol A (BPA), an endocrine-disrupting chemical, is widely present in the environment. It has been reported that perinatal exposure to low doses of BPA that are less than the tolerable daily intake level (50μg/kg/day) affects anxiety-like behavior and dopamine levels in the brain. Although the dopaminergic system in the brain is considered to be related to anxiety, no study has reported the effects of low-dose BPA exposure on the dopaminergic system in the brain and on anxiety-like behavior using the same methods of BPA exposure. To investigate the relationship between alterations in anxiety-like behavior and changes in the dopaminergic system in the brain induced by BPA, we examined the effects of BPA on anxiety-like behavior using an open field test in juvenile and adult mice and measured DA and DOPAC levels and the DOPAC/DA ratio in the dorsal hippocampus (HIP), amygdala (AMY), and medulla oblongata (MED) using high-performance liquid chromatography (HPLC) in adult mice. In males, BPA decreased the time spent in the center area of the open field in both juveniles and adults. In addition, BPA increased DA levels in the dorsal HIP and MED and decreased the DOPAC/DA ratio in the dorsal HIP, AMY, and MED in adults. The activity of monoamine oxidase (MAO)-B, the enzyme that metabolizes DA into DOPAC, was reduced in the MED. In females, those changes were not observed. These results suggest that an increase in anxiety-like behavior induced by perinatal exposure to BPA may be related to decreases in DA metabolites in the brain, and there are sex differences in those BPA effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2012; 39(2):273-9. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Auditory P50 suppression, which is assessed using a paired auditory stimuli (S1 and S2) paradigm to record the P50 mid-latency evoked potential, is assumed to reflect sensory gating. Recently, P50 suppression deficits were observed in patients with anxiety disorders, including panic disorder, post-traumatic stress disorder and obsessive-compulsive disorder, as we previously reported. The processes of fear conditioning are thought to play a role in the pathophysiology of anxiety disorders. In addition, we found that the P50 sensory gating mechanism might be physiologically associated with fear conditioning and extinction in a simple human fear-conditioning paradigm that involved a light signal as a conditioned stimulus (CS+). Our objective was to investigate the different patterns of P50 suppression in a discrimination fear-conditioning paradigm with both a CS+ (danger signal) and a CS- (safety signal). Twenty healthy volunteers were recruited. We measured the auditory P50 suppression in the control (baseline) phase, in the fear-acquisition phase, and in the fear-extinction phase using a discrimination fear-conditioning paradigm. Two-way (CSs vs. phase) Analysis of variance with repeated measures demonstrated a significant interaction between the two factors. Post-hoc LSD analysis indicated that the P50 S2/S1 ratio in the CS+ acquisition phase was significantly higher than that in the CS- acquisition phase. These results suggest that the auditory P50 sensory gating might differ according to the cognition of the properties (potentially dangerous or safe) of the perceived signal.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 01/2012; 84(1):26-32. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A central pattern generator (CPG) for swallowing in the medulla oblongata generates spatially and temporally coordinated movements of the upper airway and alimentary tract. To reveal the medullary neuronal network of the swallowing CPG, we examined the cytoarchitecture of the swallowing CPG and axonal projections of its individual neurons by extracellular recording and juxtacellular labeling of swallowing-related neurons (SRNs) in the medulla in urethane-anesthetized and paralyzed guinea pigs. Three major types of neuronal discharge patterns were identified during fictive swallowing induced by stimulation of the superior laryngeal nerve: early (burst-like activation during the pharyngeal stage), late (activation after the pharyngeal stage), and inhibited (inhibition during the pharyngeal stage) types. Sixteen neurons were successfully labeled in the nucleus tractus solitarii (NTS) and in the medullary reticular formation (RF). No motoneuron was labeled. The SRNs in the NTS had axons projecting to the NTS, RF, nucleus ambiguus, nucleus hypoglossus, and dorsal motor nucleus of the vagus on the ipsilateral side. Some NTS SRNs projected only within the NTS. The axons of SRNs in the RF projected also to the NTS, RF, motor nuclei on the ipsilateral side, and to the other side RF. These findings show anatomic substrates for the neuronal network of the CPG for swallowing, which consists of complex neuronal connections among SRNs in the NTS, RF, and motor nuclei.
The Journal of Comparative Neurology 03/2011; 519(11):2193-211. · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty-one healthy subjects were instructed to observe the mirror image of the tactile stimulation of their own hand (control condition) or an assistant's hand (experimental condition) while being queried about the referred sensation (RS) in their own masked hand behind the mirror. The rated intensity of the RS under the experimental condition was significantly stronger than that under the control condition. In a second experiment, the experimental condition was replaced with the tactile stimulation of a prosthetic (rubber) hand, and was compared with the tactile stimulation of the subject's own hand (control condition). In both of the experiments, the rated intensity of RS was significantly stronger under the experimental condition than under the control condition. The qualitative characteristics of the induced RS on the mirror image hand--including the location, sense of ownership, and various subjective feelings--were also found to vary among subjects. In conclusion, an RS could be induced in healthy subjects on the mirror image of the hand by tactile stimulations, although this effect differed substantially among individuals.
Psychological Research 01/2011; 75(1):54-60. · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several lines of evidence suggest that the N-methyl-D-aspartate (NMDA) receptor plays a significant role in fear conditioning and extinction. However, our knowledge of the role of D-serine, an endogenous ligand for the glycine site of the NMDA receptor, in fear extinction is quite limited compared to that of D-cycloserine, an exogenous partial agonist for the same site. In the current study, we examined the effects of D-serine on fear extinction and phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC) during the process of fear extinction. Systemic administrations of D-serine (2.7 g/kg, i.p.) with or without the ERK inhibitor SL327 (30 mg/kg, i.p.) to C57BL/6J mice were performed before fear extinction in a cued fear conditioning and extinction paradigm. Cytosolic and nuclear ERK 1/2 phosphorylation in the hippocampus, BLA, and mPFC were measured 1h after extinction (E1h), 24h after extinction (E24h), and 1h after recall (R1h) by Western blotting. We found that D-serine enhanced the extinction of fear memory, and the effects of D-serine were reduced by the ERK phosphorylation inhibitor SL327. The Western blot analyses showed that D-serine significantly increased cytosolic ERK 2 phosphorylation at E1h in the hippocampus and cytosolic ERK 1/2 phosphorylation at R1h in the BLA. The present study suggested that D-serine might enhance fear extinction through NMDA receptor-induced ERK signaling in mice, and that D-serine has potential clinical importance for the treatment of anxiety disorders.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2010; 34(6):895-902. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inhibitory postsynaptic potentials (IPSPs) of laryngeal motoneurons (LMs) are essential for narrowing the glottis at just the right time during swallowing, which prevents aspiration. To examine the property of IPSPs of LMs during swallowing, we monitored the effects of intracellular application of chloride ion and extracellular application of inhibitory neurotransmitter antagonists on the membrane potential trajectories of LMs during fictive swallowing in decerebrate, paralyzed cat. Adductor LMs hyperpolarized briefly at the beginning of the pharyngeal stage of swallowing (PS) and then depolarized explosively during the remaining part of the PS. Abductor LMs exhibited various patterns during swallowing; hyperpolarization during the PS followed by depolarization at the offset of the PS, slight depolarization, or plateau potentials. Chloride-dependent IPSPs were revealed during the initial part of PS in adductor LMs and during the whole PS in abductor LMs. The swallow-related IPSPs were depressed by iontophoretic extracellular application of bicuculline in both adductor and abductor LMs, but they were not modified by strychnine application. It is concluded that the swallow-related inhibition of both adductor and abductor LMs is chloride-dependent IPSPs mediated through GABA(A) receptors, not through glycine receptors.
Neuroscience Research 04/2010; 67(4):327-33. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The processes of fear conditioning and extinction are thought to be related to the pathophysiology of anxiety disorders including obsessive-compulsive disorder (OCD). We have reported alterations of auditory P50 suppression in human fear conditioning and extinction in healthy control subjects (Kurayama et al., 2009). In the study, P50 suppression was impaired transiently in the course of fear acquisition and extinction. In this study, we investigated the changes of P50 suppression with OCD patients in the course of the same experimental paradigm. 39 patients with OCD and 21 healthy control subjects were recruited. In the acquisition phase of classical fear conditioning, 10 pairings of the conditioned stimulus (CS; the visual stimulus from a light-emitting diode) and the unconditioned stimulus (US; the electrical stimulus to the wrist) were administered, and in the extinction phase, 10 CS without US were administered. P50 auditory evoked potentials were measured as the first stimulus sound (S1) and the second stimulus sound (S2) in double-click paradigm with a 500 ms interval. P50 S2/S1 ratio was used to evaluate P50 suppression. The mean P50 S2/S1 ratio in patients with OCD significantly elevated from baseline level during the fear acquisition as that in healthy controls, but the elevated S2/S1 ratio did not recover to baseline level. The S2/S1 ratio in the extinction phase was significantly higher in the OCD patient group than in the healthy control group. In conclusion, our data suggested that P50 sensory gating in fear extinction was impaired in patients with OCD.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2010; 34(2):317-22. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Based on NMDA hypofunction hypothesis for negative symptoms and cognitive deficits in schizophrenia, MK-801-induced animal models of schizophrenia may help us understand the different effects between typical and atypical antipsychotics. On the other hand, the mitogen-activated protein kinase (MAPK) signaling pathways may participate in antipsychotic actions. The aim of this study was to investigate the effects of aripiprazole on MK-801-induced prepulse inhibition (PPI) disruption and MAPK phosphorylation in mice. To clarify the effects of aripiprazole on MK-801-induced PPI disruption, we measured PPI of 51 ddY male mice after aripiprazole was administered 15 min prior to the injection of MK-801, and measured activation of cytosol and nuclear MAPK phosphorylation by western blotting. Aripiprazole (4.0 mg/kg) significantly reversed the MK-801 (0.15 mg/kg)-induced PPI deficits. Pretreatment of aripiprazole (40 mg/kg) had a tendency to suppress MK-801 (1.0 mg/kg)-induced pMEK/MEK (Ser218/222) activation. In addition, aripiprazole treatment showed a significant decrease of pERK/ERK. Our data suggested that aripiprazole may reverse MK-801-induced PPI deficits through regulation of MAPK phosphorylation in the same way as the atypical antipsychotic drug, clozapine.
[Show abstract][Hide abstract] ABSTRACT: The forebrain is one of the important suprapontine micturition centres. Previous studies have shown that electrical stimulation of the frontal lobe and the anterior cingulate gyrus elicited either inhibition or facilitation of bladder contraction. Patients with frontal lobe tumours and aneurysms showed micturition disorders. Functional brain imaging studies showed that several parts of the forebrain are activated during bladder filling. We aimed to examine neuronal activities of forebrain structures with respect to bladder contraction in cats. In 14 adult male cats under ketamine anaesthesia in which a spontaneous isovolumetric bladder-contraction/relaxation cycle had been generated, we carried out extracellular single-unit recording in forebrain with respect to the contraction/relaxation cycles in the bladder. We recorded 112 neurons that were related to the bladder-contraction/relaxation cycles. Ninety-four neurons were found to be tonically activated during the bladder-relaxation phase, whereas the remaining 18 neurons were tonically activated during the bladder-contraction phase. Both types of neuron were widely distributed around the cruciate sulcus. Most were located medially (medial and superior frontal gyrus) and the rest were located laterally (middle and inferior frontal gyrus). Neurons recorded in forebrain structures were activated with respect to the contraction/relaxation cycles in the bladder. Forebrain structures may have a significant role in regulating bladder contraction in cats.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to determine whether murines could be substituted for traditional experimental mammals to study the brainstem mechanism of vocalization. We conducted systematic electrical and chemical stimulation of the brainstem in guinea pigs to identify the similarities in the call sites between murines and other mammals. We further examined whether or not fictive vocalization could be induced in paralyzed guinea pigs, an experimental model which facilitates neuronal recording in the brainstem. The sites where electrical stimulation evoked vocalization were distributed continuously from the periaqueductal grey (PAG) to the lower brainstem. This call area usually ended at the most caudal part of the inferior olive and thus did not continuously extend to the nucleus retroambiguus. Microinjections of d,l-homocysteic acid and bicuculline induced vocalization at the PAG, parabrachial nucleus, and the most dorsal part of the pontine reticular formation. The brainstem call areas and vocal motor patterns induced from these areas were approximately consistent with those in other mammals. Fictive vocalization induced by PAG stimulation could be identified from activities of the phrenic, abdominal, and superior laryngeal nerves in paralyzed guinea pigs. We thus concluded that guinea pigs can be utilized in studies of brainstem vocal mechanism.
Neuroscience Research 12/2009; 66(4):359-65. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease (PD) affects the nigrostriatal projections leading to micturition disturbance in most cases. Overactive bladder (OAB) symptoms such as urinary urgency or urgent urinary incontinence are common amongst PD patients. Several urodynamic studies have revealed that detrusor overactivity causes OAB symptoms in PD patients. We assert that striatal dysfunction might contribute to the pathogenesis of detrusor overactivity in PD patients. However, the role of the striatum in bladder contraction remains unclear.
We generated spontaneous isovolumetric bladder contractions in 12 ketamine-anesthetized adult male cats and subsequently performed electrical stimulation and extracellular single-unit recording in the striatum.
Electrical stimulation applied to the posterior ventral caudate nucleus and the adjacent putamen reduced inhibition of the spontaneous bladder contraction. None of the responses were facilitatory. Electrical stimulation was most effective at an amplitude of 70-400 microA. Forty-six neurons that exhibited correlation to spontaneous bladder contraction were recorded in the striatum. Thirty-five neurons were found to be tonically active throughout the bladder relaxation phase, and the remaining 11 neurons were active during the bladder contraction phase. These particular neurons were located within the area in which spontaneous bladder contraction was inhibited by electrical stimulation.
Electrical stimulation was found to inhibit bladder contraction, and a correlation was observed between spontaneous bladder relaxation/contraction and neuronal firing in the posterior ventral striatum.
Neurourology and Urodynamics 03/2009; 28(6):549-54. · 2.67 Impact Factor