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Taketoshi Ono

Publications and source records attributed to Taketoshi Ono.

30 records · Page 2Linked to original sources

Representation of place by monkey hippocampal neurons in real and virtual translocation.

The hippocampal formation (HF) is hypothesized as a neuronal substrate of a cognitive map, which represents environmental spatial information by an ensemble of neural activity. However, the relationships between the hippocampal place cells and the cognitive map have not been clarified in monkeys. The present study was designed to investigate how activity patterns of place-selective neurons encode spatial relationships of various environmental stimuli; to do this, we used multidimensional scaling (MDS) for hippocampal neuronal activity in the monkey during the performance of real and virtual translocation. Of 389 neurons recorded from the monkey HF and parahippocampal gyrus (PH), 166 had place fields that displayed increased activity in a specific area of an experimental field and/or on a monitor (place-selective neurons). The MDS transformed relationships among the 16 places in the experimental field and the monitor, expressed as correlation coefficients between all possible pairs of two places based on the 166 place-selective responses, into geometric relationships in a two-dimensional MDS space. In the real translocation tasks, the 16 places were distributed throughout the MDS space, and their relative positions were well correlated to real positions in the experimental laboratory. However, the correlation between the MDS space and real arrangements was significantly smaller in virtual than real translocation tasks. The present results strongly suggest that activity patterns of the HF and PH neurons represent spatial information and might provide a neurophysiological basis for a cognitive map.

Animals↗

Regulated transgene delivery by ganciclovir in the brain without physiological alterations by a live attenuated herpes simplex virus vector.

The distribution of a live attenuated herpes simplex virus (betaH1)-mediated gene delivery into the central nervous system (CNS) was regulated by growth inhibition with ganciclovir (GCV) and the effect of this transgene expression system on the physiologic response was characterized by the acoustic startle response and its prepulse inhibition. We inoculated betaH1 expressing beta-galactosidase (beta-gal) driven by the latency associated transcripts promoter into the right caudate putamen of rats. Histochemical analysis demonstrated that the inoculation of betaH1 in the right caudate putamen resulted in a high level of beta-gal expression in the neurons of the area projecting to the inoculation site. On 14 days after inoculation without GCV-treatment, beta-gal activity localized in the anterior olfactory nucleus, frontal, insular, orbital, parietal, perirhinal, piriform cortices and the temporal region including the amygdala. In contrast, the distribution of beta-gal activity was regulated by the interval between virus inoculation and GCV-treatment and maintained after its cessation without significant alteration. The whole process of transgene expression did not influence the emotional behavior, indicating that this vector system is a suitable model for analyzing the transgene function or applying the gene therapy for the CNS diseases.

Animals↗

A method for accurate determination of stereotaxic coordinates in single-unit recording studies in monkeys by high-resolution three-dimensional magnetic resonance imaging.

For single-unit recording from the brain in monkeys, the precise determination of recording targets is essential. Although magnetic resonance imaging (MRI) has been used recently in several laboratories, it has been difficult to obtain three-dimensional information on a target from two-dimensional pictures, and, therefore, it has also been difficult to determine precise coordinates. We developed a new method for precisely determining target-area coordinates based on reconstructed rendering pictures made from three-dimensional MRI data. We also combined this method with magnetic resonance angiography to avoid severe vessel complications in recording experiments.

Animals↗

Age-dependent changes in electroencephalographic responses to alcohol consumption in subjects with aldehyde dehydrogenase-2 genetic variations.

BACKGROUND: We have recently reported that alcohol consumption resulted in a significant increase in alpha power of the EEGs in aldehyde dehydrogenase-2 (ALDH2)-normal (NN) subjects but not in ALDH2-deficient heterozygote (ND) subjects. The purpose of the present study was to investigate interactive effects of individual factors such as age and ALDH2 genotype on alcohol-induced EEG changes. METHODS: We examined EEG power spectral changes induced by 0.4 ml/kg of alcohol ingestion in 53 NN and 21 ND subjects of two different age groups: younger and older groups. Blood ethanol and acetaldehyde levels were also determined in 17 NN and 13 ND subjects in separate studies. RESULTS: Alcohol consumption markedly increased EEG power in the NN subjects of the older group, especially in theta and slow alpha power, whereas only slight increases were noted in fast alpha and beta power in the NN subjects of the younger group. However, no such differences between the two age groups were observed in the ND subjects. It should be noted that there were no differences in blood ethanol and acetaldehyde level at 30 min after alcohol ingestion between the different age groups in both genotypes. However, there was a significant increase in frequency of alcohol intake in the older group of both genotype groups. The multiple regression analysis indicated that both alcohol use habits and genotype, as well as aging, significantly modulated EEG changes after alcohol ingestion. CONCLUSIONS: The results suggest that both ALDH2 genotype and age as well as alcohol use habits modify alcohol sensitivity in the central nervous system, resulting in greater increases in EEG energy in response to alcohol intake in the older group of the NN subjects.

Acetaldehyde↗

Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects.

The present study was designed to investigate the effects of aldehyde dehydrogenase-2 (ALDH2) genotype on cardiovascular and endocrine responses to alcohol ingestion in young, healthy Japanese subjects. For this purpose, we monitored changes in the electrocardiogram (ECG), blood pressure (BP), finger blood flow (BF) and facial skin temperature (FST) during and after alcohol ingestion (0.4 ml/kg body weight). Spectral analyses of beat-to-beat variations of heart rate (HR), BP and BF were applied. Two major spectral components were examined at low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-10.4 Hz) bands for HR and BP variability (BPV). Significant effects for ALDH2 genotype were observed in HR variability (HRV) analysis; HF power of HRV was markedly depressed and the LF/HF ratio was significantly higher with alcohol in ALDH2-deficient (ND) subjects, while ALDH2-normal (NN) subjects did not display such changes. Analysis of BP variability showed increased LF and HF power after alcohol ingestion in the NN subjects, but there were no significant differences between genotypic groups. We also examined BF variability (BFV) in six major spectral components; power of the 0.8-2.2 Hz frequency band was significantly affected by genotype and higher power was observed in the ND subjects. Plasma concentrations of both epinephrine and norepinephrine increased after alcohol ingestion only in the ND subjects. Furthermore, plasma concentrations and urinary excretion of epinephrine, but not norepinephrine, were higher after alcohol ingestion in the ND than in the NN subjects. Blood acetaldehyde levels were about 10-fold higher in the ND than in the NN subjects although blood alcohol levels similarly increased in the ND and NN subjects. Our results also indicated that alcohol ingestion increased secretion of pituitary-adrenal hormones including ACTH, beta-endorphin and cortisol in the ND subjects. The present results along with previous studies suggest that alcohol-induced tachycardia in the ND subjects was probably mediated by acetaldehyde-induced rise in epinephrine secretion from the adrenal medulla and/or changes in the autonomic nervous system. Alcohol-induced relative predominance of cardiac sympathetic activity in the ND subjects might be ascribed partly to increased norepinephrine secretion from sympathetic nerve terminals. Effects of acetaldehyde on these cardiovascular and endocrine systems were discussed in terms of their effects on the central nervous system.

Adult↗

Spatio-temporal dynamics of brain activated regions during drinking behavior in rats.

Spatio-temporal dynamics of activated brain areas induced by drinking were investigated and visualized in behaving rats using functional magnetic resonance imaging (fMRI). The rats were trained to drink in the magnet bore, and the images were taken during and after drinking glucose and distilled water. During glucose ingestion, the signal intensity was increased continuously and maximally in the lateral hypothalamic area (LHA) and the ventromedial hypothalamus (VMH). Somewhat less intense activation in the central nucleus of the amygdala (AMc), and transient activation in the piriform cortex and the mediodorsal nucleus of the thalamus were observed. The signal intensities of other regions measured were largely unchanged. During post-ingestive periods, the signals re-increased in the hypothalamic areas and AMc. When water was given, LHA and VMH were similarly activated, however, the signal intensity in the amygdala was not significantly increased. The results indicate that these brain regions are activated differentially during drinking behavior, and that LHA and VMH play a central role in the control of not only feeding but also drinking. The regional activities in LHA and VMH are not principally related to the gustatory sensation, and the reactivation after drinking may be related to satisfaction or post-ingestive nutritional information. Also, the responses of AMc are probably due to reward value difference. To the best of our knowledge, this is the first report of mapping of brain areas using fMRI in behaving rats. The improved method described in this study for collecting fMRI data in behaving animals will be useful for studying functional network during animal behavior.

Animals↗

Altered accumbens neural response to prediction of reward associated with place in dopamine D2 receptor knockout mice.

Midbrain dopaminergic activity seems to be important in forming the prediction of future events such as rewards. The nucleus accumbens (NAc) plays an important role in the integration of reward with motor function, and it receives dense dopamine innervation and extensive limbic and cortical afferents. Here, we examined the specific role of the dopamine D2 receptor (D2R) in mediating associative learning, locomotor activity, and regulating NAc neural responses by using D2R-knockout (KO) mice and their wild-type littermates. D2R-KO mice displayed reduced locomotor activity and slower acquisition of a place-learning task. D2R-KO eliminated the prereward inhibitory response of neurons in the NAc. In contrast, an increased number of neurons in D2R-KO mice displayed place-related activity. These results provide evidence that D2R in the NAc participates in coding for a specific type of neural response to incentive contingencies and partly in spatial learning.

Animals↗

Synapses on GABAergic neurons in the basolateral nucleus of the rat amygdala: double-labeling immunoelectron microscopy.

Although the basolateral nucleus (BL) of the amygdala is known to contain an abundance of gamma-aminobutyric acid (GABA)ergic neurons that regulate the amygdaloid projection neurons and influence storage and consolidation of memory, it remains to be determined what type of neuronal input controls GABAergic neurons in the BL. We examined the synapses that GABAergic neurons form with GABAergic and noradrenergic neurons and terminals with unknown transmitters by double-labeling immunoelectron microscopy using anti-GABA and dopamine-beta-hydroxylase (DBH) antisera. The medium and small dendrites of the GABAergic neurons were shown to receive symmetric, inhibitory-type synapses from GABAergic axon terminals and asymmetric, excitatory-type synapses from noradrenergic axon terminals. Each segment of the GABAergic neurons from perikarya to dendritic spines received both symmetric and asymmetric synapses from unlabeled axon terminals of various forms and sizes. The incidence rates of the two types of synapses were almost identical. Our results suggest that GABAergic neurons in the BL of the rat amygdala might be affected by the excitatory influence of the noradrenergic system and the inhibitory influence of the GABAergic system. Furthermore, these neurons are also strongly influenced by both excitatory and inhibitory-type synapses from neuronal systems other than the GABAergic and noradrenergic systems.

Amygdala↗

Effects of a novel arginine-vasopressin derivative, NC-1900, on the spatial memory impairment of rats with transient forebrain ischemia.

NC-1900, an arginine-vasopressin derivative, has been reported to enhance memory for avoidance behavior. Specifically, NC-1900 ameliorated cycloheximide-induced learning impairments in a passive avoidance test in rats. In the present study, we investigated that effects of NC-1900 on place learning in rats with selective lesions in the CA1 subfield of the hippocampal formation produced by transient forebrain ischemia. NC-1900 was administered daily (1 microg/kg, p.o.) 1 h before the place learning task. A rat was required to alternate between 2 small circular areas located diametrically opposite each other on the circumference of an open field in order to obtain intracranial electrical stimulation reward (the spatial navigation task). Rats with hippocampal lesions showed severe place learning impairments both in task performance (indicated by number of rewards obtained per a session) and in navigation performance (forming efficient trails) over the 30-day test period. Treatment with NC-1900 ameliorated deficits in the place learning exhibited by rats with the same hippocampal lesions, such that their performance reached normal levels. There were no significant differences in the ischemic hippocampal lesions, spontaneous locomotor activity, and stimulation current intensity between the treated and untreated rats. The results demonstrated that NC-1900 reduced place learning impairments produced by hippocampal lesions.

Amnesia↗

Generators of visual evoked potentials for faces and eyes in the human brain as determined by dipole localization.

Human visual evoked potentials were recorded during presentation of photos of human and animal faces and various face features. Negative waves with approximate peak latencies of 165 msec (N170) were bilaterally recorded from the occipito-temporal regions. Mean peak latencies of the N170 were shorter for faces than eyes only. Analyses of amplitudes of evoked potentials indicated that the N170 elicited by faces reflected activity of a specific neural system which was insensitive to detailed differences among individual faces regardless of species, and consequently suggest that this system might function to detect existence of faces in general. On the other hand, the mean amplitude of the N170 elicited by human eyes was significantly larger than those by animal eyes. These differences in response latencies and amplitudes of the N170 suggest existence of at least 2 different visual evoked potentials with similar latencies (i.e., N170) which are sensitive to faces in general and human eyes, respectively. Dipole source localization analysis indicated that dipoles for the N170 elicited by eyes were located in the posterior inferior temporal gyrus, and those for faces, located initially in the same region, but moved toward the fusiform and lingual gyri at the late phase of the N170. The results indicated that information processing of faces and eyes separated at least as early as the latency of the N170 at the posterior inferior temporal gyrus as well as the fusiform and lingual gyri, and might provide neurophysiological and anatomical bases to an initial structural encoding stage of human faces.

Adult↗

Neuronal responses of the rat amygdala during extinction and reassociation learning in elementary and configural associative tasks.

To investigate functional heterogeneity within the amygdala in appetitive conditioned instrumental behaviours, neuronal activity was recorded from the amygdala of behaving rats during learning and discrimination of conditioned sensory stimuli associated with or without reinforcement [sucrose solution, intracranial self-stimulation (ICSS)]. Sensory stimuli included auditory (tone), visual (light) and configural (simultaneous presentation of tone and light) stimuli. The rat was trained to lick a spout protruded close to its mouth just after a conditioned sensory stimulus to obtain a reward. Of the 609 neurons recorded from the amygdala and amygdalostriatal transition area, 154 responded to one or more sensory stimuli. The 62 amygdalar neurons responded strongly to certain conditioned sensory stimuli associated with rewards. Of these 62 neurons, 45 were tested with the extinction trials. Responses of 31 neurons to conditioned stimuli were finally extinguished, and those of the remaining 14 were not extinguished. Furthermore, responses of 26 of these 31 neurons resumed in the relearning trials (plastic neurons), suggesting that these sensory responses were associative rather than just responses to physical properties of the stimuli. These plastic neurons were located mainly in the basolateral nucleus of the amygdala, and responses of the plastic neurons were correlated with behavioural responses. These results suggest that the basolateral nucleus is crucial in associative learning between sensory information and affective significance for behavioural outputs in appetitive conditioned instrumental behaviours.

Acoustic Stimulation↗

Comparison of brain activity between dopamine D2 receptor-knockout and wild mice in response to dopamine agonist and antagonist assessed by fMRI.

It has been reported that antipsychotic dopamine-D2-receptor (D2R) antagonists affected other neurotransmitter systems. In the present study, the effects of a D2R agonist, bromocriptine, and a D2R antagonist, spiperone, on brain activity were investigated using wild-type mice (WT) with intact D2Rs, and D2R-knockout mice (D2R-KO) lacking D2Rs by functional magnetic resonance imaging. In the WT, flow-weighted signal intensity significantly increased after administration of bromocriptine in the hippocampal formation. In contrast, signal intensity significantly decreased after administration of spiperone in the somatosensory-motor cortices, thalamus, anterior cingulate cortex, caudate-putamen, nucleus accumbens, hippocampal formation, and amygdala. In the D2R-KO, however, no significant changes were observed after administration of either bromocriptine or spiperone. The present results indicated that the D2R-KO lacked sensitivity to D2R agonist and antagonist in agreement with its genetic defects, which confirmed that the changes in brain activity in the WT after administration of either drug were mediated through D2Rs. These results suggest that antipsychotic D2R antagonists affect activity of the same brain regions of human patients through D2Rs, as observed in the present study. These changes in brain activity might be related to therapeutic efficacy as well as side effects of antipsychotic drugs on schizophrenic patients.

Animals↗