Biomedical subjects

Masahiko Takada

Publications and source records attributed to Masahiko Takada.

At least 19 recordsLinked to original sources

PubMed2006

Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of spikes in rat mesencephalic trigeminal neurons.

The axon initial segment plays important roles in spike initiation and invasion of axonal spikes into the soma. Among primary sensory neurons, those in the mesencephalic trigeminal nucleus (MTN) are exceptional in their ability to initiate soma spikes (S-spikes) in response to synaptic inputs, consequently displaying two kinds of S-spikes, one caused by invasion of an axonal spike arising from the sensory receptor and the other initiated by somatic inputs. We investigated where spikes are initiated in such MTN neurons and whether there are any differences between the two kinds of S-spikes. Simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-backpropagation from the spike-initiation site in the stem axon to the soma in response to 1-ms somatic current pulse, which disclosed the delayed emergence of S-spikes after the current-pulse offset. These initiated S-spikes were smaller in amplitude than S-spikes generated by stimulation of the stem axon; however, 4-AP (< or =0.5 mM) eliminated the amplitude difference. Furthermore, 4-AP dramatically shortened the delay in spike initiation without affecting the spike-backpropagation time in the stem axon, whereas it substantially prolonged the refractory period of S-spikes arising from axonal-spike invasion without significantly affecting that of presumed axonal spikes. These observations suggest that 4-AP-sensitive K(+) currents exert two opposing effects on S-spikes depending on their origins: suppression of spike initiation and facilitation of axonal-spike invasion at higher frequencies. Consistent with these findings, strong immunoreactivities for Kv1.1 and Kv1.6, among 4-AP-sensitive and low-voltage-activated Kv1 family examined, were detected in the soma but not in the stem axon of MTN neurons.

4-Aminopyridine↗

PubMed2005

Comparable GABAergic mechanisms of hippocampal seizurelike activity in posttetanic and low-Mg2+ conditions.

It is known that GABA is a major inhibitory neurotransmitter in mature mammalian brains, but the effect of this substance is sometimes converted into depolarizing or even excitatory when the postsynaptic Cl- concentration becomes high. Recently we have shown that seizurelike afterdischarge induced by tetanic stimulation in normal extracellular fluid (posttetanic afterdischarge) is mediated through GABAergic excitation in mature hippocampal CA1 pyramidal cells. In this study, we examined the possible contribution of similar depolarizing/excitatory GABAergic input to the CA1 pyramidal cells to the seizurelike afterdischarge induced in a low extracellular Mg2+ condition, another experimental model of epileptic seizure activity (low-Mg2+ afterdischarge). Perfusion of the GABAA antagonist bicuculline abolished the low-Mg2+ afterdischarge, but not the interictal-like activity, in most cases. Each oscillatory response during the low-Mg2+ afterdischarge was dependent on Cl- conductance and contained an F- -insensitive depolarizing component in the pyramidal cells, thus indicating that the afterdischarge response may be mediated through both GABAergic and nonGABAergic transmissions. In addition, local GABA application to the recorded cells revealed that GABA responses were indeed depolarizing during the low-Mg2+ afterdischarge. Furthermore, the GABAergic interneurons located in the strata pyramidale and oriens fired in oscillatory cycles more actively than those in other layers of the CA1 region. These results suggest that the depolarizing GABAergic input may facilitate oscillatory synchronization among the hippocampal CA1 pyramidal cells during the low-Mg2+ afterdischarge in a manner similar to the expression of the posttetanic afterdischarge.

Action Potentials↗

PubMed2005

Input-output organization of jaw movement-related areas in monkey frontal cortex.

The brain mechanisms underlying mastication are not fully understood. To address this issue, we analyzed the distribution patterns of cortico-striatal and cortico-brainstem axon terminals and the origin of thalamocortical and intracortical fibers by injecting anterograde/retrograde tracers into physiologically and morphologically defined jaw movement-related cortical areas. Four areas were identified in the macaque monkey: the primary and supplementary orofacial motor areas (MIoro and SMAoro) and the principal and deep parts of the cortical masticatory area (CMaAp and CMaAd), where intracortical microstimulation produced single twitch-like or rhythmic jaw movements, respectively. Tracer injections into these areas labeled terminals in the ipsilateral putamen in a topographic fashion (MIoro vs. SMAoro and CMaAp vs. CMaAd), in the lateral reticular formation and trigeminal sensory nuclei contralaterally (MIoro and CMaAp) or bilaterally (SMAoro) in a complex manner of segregation vs. overlap, and in the medial parabranchial and Kölliker-Fuse nuclei contralaterally (CMaAd). The MIoro and CMaAp received thalamic projections from the ventrolateral and ventroposterolateral nuclei, the SMAoro from the ventroanterior and ventrolateral nuclei, and the CMaAd from the ventroposteromedial nucleus. The MIoro, SMAoro, CMaAp, and CMaAd received intracortical projections from the ventral premotor cortex and primary somatosensory cortex, the ventral premotor cortex and rostral cingulate motor area, the ventral premotor cortex and area 7b, and various sensory areas. In addition, the MIoro and CMaAp received projections from the three other jaw movement-related areas. Our results suggest that the four jaw movement-related cortical areas may play important roles in the formation of distinctive masticatory patterns.

Animals↗

PubMed2005

Organization of multisynaptic inputs from prefrontal cortex to primary motor cortex as revealed by retrograde transneuronal transport of rabies virus.

The organization of multisynaptic projections from the prefrontal cortex to the primary motor cortex (MI) was examined in macaque monkeys by retrograde transneuronal transport of rabies virus. In the first series of experiments, the virus was injected into the MI forelimb region, and the time-dependent distribution patterns of transsynaptic labeling were analyzed in the frontal lobe with various survivals (2-4 d). Two days after the viral injection, neuronal labeling emerged in the caudal aspects of the nonprimary motor-related areas that are known to project to the MI directly. At the same time, the motor thalamus contained labeled neurons. On the third day, cortical labeling extended into the rostral motor-related areas and, also, prearcuate area 8. Moreover, a number of labeled neurons were located in the internal pallidum and the cerebellar nuclei. At the 4 d postinjection period, neuronal labeling occurred widely in prefrontal areas as well as in the putamen and the cerebellar cortex. In the second series of experiments, the viral injection was made into the MI hindlimb region, and the distribution pattern of prefrontal labeling on the fourth day was compared with that in the forelimb-injection case. The labeled neurons in each prefrontal area were much fewer in the hindlimb-injection case than in the forelimb-injection case. Whereas ventral area 46 was most densely labeled from the forelimb region, only sparse labeling from the hindlimb region was observed in this prefrontal area. The present results suggest the importance of ventral area 46 in the cognitive control of forelimb movements.

Animals↗

PubMed2005

Region-specific modulation of electrically induced synchronous oscillations in the rat hippocampus and cerebral cortex.

Strong tetanization induces synchronous membrane potential oscillations (seizure-like afterdischarge) in mature pyramidal cells of the hippocampal CA1 region. To investigate whether local networks in other brain regions can generate such an afterdischarge independently, we studied the inducibility of afterdischarge in individual 'isolated slices' of the rat hippocampal CA1 and CA3 regions, dentate gyrus (DG), entorhinal cortex (EC), and temporal cortex (TC) using intracellular and extracellular recordings. The strong tetanization constantly induced afterdischarges in the CA1 and CA3 pyramidal cells as well as in the EC and TC superficial principal cells. However, parameters of the afterdischarges, such as the frequency and duration of afterdischarges, varied among the regions. A mixture of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or a GABA(A) receptor antagonist completely blocked the afterdischarges. Local GABA application during the afterdischarge elicited depolarization, rather than hyperpolarization. Moreover, reversal potentials of the afterdischarge were around -40 mV. In contrast, the tetanization resulted in occasional afterdischarge-like activities in DG slices, which were blocked by the non-NMDA or GABA(A) receptor antagonist. These findings suggest that the afterdischarges mediated through the excitatory GABAergic and glutamatergic transmissions might be common to, but be modulated differently by individual local networks in the hippocampus and cortex.

Animals↗

PubMed2004

Synaptic interactions between pyramidal cells and interneurone subtypes during seizure-like activity in the rat hippocampus.

We have recently reported that excitatory GABAergic and glutamatergic mechanisms may be involved in the generation of seizure-like (ictal) rhythmic synchronization (afterdischarge), induced by a strong synaptic stimulation of the CA1 pyramidal cells in the mature rat hippocampus in vitro. To clarify the network mechanism of this neuronal synchronization, dual whole-cell patch-clamp recordings of the afterdischarge responses were performed simultaneously from a variety of interneurones and their neighbouring pyramidal cells in hippocampal CA1-isolated slice preparations. According to morphological and electrophysiological criteria, the recorded interneurones were then classified into distinct subtypes. The non-fast-spiking interneurones located in the strata lacunosum-moleculare and radiatum hardly discharged during the afterdischarge, whereas most of the fast-spiking and non-fast-spiking interneurones in the strata oriens and pyramidale, including the basket, chandelier and bistratified cells, exhibited prominent firings that were precisely synchronous with oscillatory responses in the pyramidal cells. Field potential recordings showed that excitatory synaptic transmissions might take place primarily in the strata oriens and pyramidale during the afterdischarge. Restricted lesions in the strata oriens and pyramidale, but not in the other layers, resulted in the complete desynchronization of afterdischarge activity, and also, local application of glutamate receptor antagonists to these layers blocked the expression of afterdischarge. The present findings indicate that the neuronal synchronization of epileptic afterdischarge may be accomplished in a 'positive feedback circuit' formed by the excitatory GABAergic interneurones and the glutamatergic pyramidal cells within the strata oriens and/or pyramidale of the hippocampal CA1 region.

2-Amino-5-phosphonovalerate↗

PubMed2004

Prognostic value of ECG-gated thallium-201 single-photon emission tomography in patients with coronary artery disease.

BACKGROUND: The phenomenon of reversible impairment in LV function has been well described and is known as myocardial stunning. OBJECTIVE: Thallium-201 myocardial perfusion gated SPECT was used to evaluate myocardial stunning and its incremental prognostic value in patients with coronary artery disease. PATIENTS AND METHODS: Fifty-six patients (aged 63+/-11 years) with coronary artery disease were included in this study. All subjects underwent exercise thallium scintigraphy. ECG-gated SPECT was obtained both at post-stress (10 minutes after the injection of 111 MBq of thallium at the time of peak exercise) and at rest (180 minutes). The left ventricular ejection fraction (LVEF) and end-systolic and end-diastolic volume (ESV, EDV) were determined by a quantitative gated SPECT (QGS) program. RESULTS: Follow-up was complete in all patients (mean 569 days). The magnitude of the depression of post-stress LVEF relative to the rest LVEF was correlated with the severity of ischemia (p < 0.05). The group with a median LVEF of more than 45% had a significantly higher event-free rate (p < 0.01). CONCLUSION: Assessment of post-stress left ventricular function by gated-SPECT provides incremental prognostic information and is useful in predicting cardiac events in patients with suspected or definite coronary artery disease.

Causality↗

PubMed2004

Input-output organization of the rostral part of the dorsal premotor cortex, with special reference to its corticostriatal projection.

Until recently, little was known about the rostral part of the dorsal premotor cortex (PMdr). In the present study, somatotopical representations of the PMdr were electrophysiologically identified in the macaque monkey, and the distribution of corticostriatal input from the forelimb region of the PMdr was analyzed in relation to its thalamocortical and intracortical (with the frontal lobe) connections. Results have revealed that (1) the forelimb is represented predominantly in the PMdr, while only a few sites representing other body parts are distributed as embedded within the forelimb representation; (2) the corticostriatal input zone is located in the striatal cell bridges and their surroundings; (3) the cells of origin of the thalamocortical projections to the PMdr are located mainly in the parvicellular division of the ventroanterior nucleus, the oral divison of the ventrolateral nucleus, area X, the caudal divison of the ventrolateral nucleus, the mediodorsal nucleus, and the intralaminar nuclear group; (4) the PMdr is interconnected primarily with higher-order motor-related areas and dorsal area 46. These data indicate that the input-output pattern of the PMdr resembles those of the presupplementary motor area and the rostral cingulate motor area, and that the PMdr may play critical roles in higher-order motor functions.

Action Potentials↗

PubMed2004

Neural mechanisms of versatile functions in primate anterior cingulate cortex.

The anterior cingulate cortex (ACC) is located on the medial wall of the cerebral hemisphere in humans and non-human primates, and has well developed intracortical and subcortical connections. Recent brain-imaging studies have suggested the possible involvement of the ACC in a variety of cognitive and motor-related functions. To clarify the cellular mechanisms underlying such higher-order functions in the ACC, neuronal activity in distinct areas of the ACC and its adjacent cingulate areas has been examined, through single unit recordings, in monkeys performing specific tasks. Each of the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas basically participates in motor-related functions such as preparation and execution of movements. In particular, the CMAr appears to be involved in selection of appropriate motor responses as well as in planning of sequential movements. Furthermore, the CMAr and area 32 may participate in attentional functions which are necessary to select correct actions. These areas have also been implicated in detection of error actions and/or monitoring of action performance. Finally, a number of neurons in the ACC exhibit specific or modulated activity relevant to reward expectation. The primate ACC may play critical roles in performing appropriate actions with attention and in checking the performance to acquire rewards efficiently.

Animals↗

PubMed2004

Scintigraphic evaluation of cardiac metabolism in multicentric Castleman's disease.

A 72-year-old woman had insidious onset of heart failure, and was diagnosed as multicentric Castleman's disease. She underwent myocardial imaging with technetium-99m tetrofosmin, 1-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP). Technetium-99m tetrofosmin studies showed almost normal uptake of the left ventricular myocardium indicating normal myocardial perfusion. 1-123 BMIPP showed reduced uptake in the apical segment of the myocardium, indicating regional fatty acid metabolic abnormalities.

Aged↗

PubMed2004

[A-1000].

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Bone Density↗

PubMed2003

Neural coding of "attention for action" and "response selection" in primate anterior cingulate cortex.

Noninvasive imaging techniques showed that the anterior cingulate cortex is related to higher-order cognitive and motor-related functions in humans. To elucidate the cellular mechanism of such cingulate functions, single-unit activity was recorded from three cingulate motor areas of macaque monkeys performing delayed conditional Go/No-go discrimination tasks using spatial (location) and nonspatial (color) visual cues. Unlike prefrontal neurons, only a few neurons coded the visual information on individual features (e.g., "left" or "red") in all of the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas. Instead, many neurons in the CMAr exhibited the attention-like activity anticipating the second (conditioned) visual cues, with the specificity to visual category ("location" or "color"). In addition, there were a number of CMAr neurons specific to motor response (Go or No-go) in relation to the second visual cues. Some of the visual category-specific neurons in the CMAr further displayed the motor response-specific activity. On the other hand, many of the task-related CMAd and CMAv neurons seemed to be implicated directly in motor functions, such as preparation and execution of movements in Go trials. The present results suggest that the CMAr neurons may participate in cognitive and motor functions of "attention for action" and "response selection" for an appropriate action according to an intention, whereas the CMAd and CMAv neurons may be involved in "motor preparation and execution".

Animals↗

PubMed2003

Thalamocortical and intracortical connections of monkey cingulate motor areas.

Although there has been an increasing interest in motor functions of the cingulate motor areas, data concerning their input organization are still limited. To address this issue, the patterns of thalamic and cortical inputs to the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas were investigated in the macaque monkey. Tracer injections were made into identified forelimb representations of these areas, and the distributions of retrogradely labeled neurons were analyzed in the thalamus and the frontal cortex. The cells of origin of thalamocortical projections to the CMAr were located mainly in the parvicellular division of the ventroanterior nucleus and the oral division of the ventrolateral nucleus (VLo). On the other hand, the thalamocortical neurons to the CMAd/CMAv were distributed predominantly in the VLo and the oral division of the ventroposterolateral nucleus-the caudal division of the ventrolateral nucleus. Additionally, many neurons in the intralaminar nuclear group were seen to project to the cingulate motor areas. Except for their well-developed interconnections, the corticocortical projections to the CMAr and CMAd/CMAv were also distinctively preferential. Major inputs to the CMAr arose from the presupplementary motor area and the dorsal premotor cortex, whereas inputs to the CMAd/CMAv originated not only from these areas but also from the supplementary motor area and the primary motor cortex. The present results indicate that the CMAr and the caudal cingulate motor area (involving both the CMAd and the CMAv) are characterized by distinct patterns of thalamocortical and intracortical connections, reflecting their functional differences.

Animals↗

PubMed2003

Differential expression patterns of mGluR1 alpha in monkey nigral dopamine neurons.

The expression pattern of metabotropic glutamate receptor 1alpha (mGluR1alpha) was immunohistochemically investigated in substantia nigra dopaminergic neurons of the macaque monkey. In normal monkeys, mGluR1alpha immunoreactivity was weakly observed in the dorsal tier of the substantia nigra pars compacta (SNc-d) where calbindin-D28k-containing dopaminergic neurons invulnerable to parkinsonian degeneration are specifically located. On the other hand, mGluR1alpha was strongly expressed in the ventral tier of the substantia nigra pars compacta (SNc-v). In monkeys treated with the parkinsonism-inducing drug, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), mGluR1alpha expression was decreased in dopaminergic neurons in the SNc-v that were spared its toxic action. These results suggest that mGluR1alpha expression may be involved at least partly in the vulnerability of dopaminergic neurons to parkinsonian insults.

Animals↗

PubMed2003

Activity and distribution patterns of monkey pallidal neurons in response to peripheral nerve stimulation.

The response patterns of pallidal neurons to electrical stimulation of the median and tibial nerves were examined in awake monkeys. Around 30% of the recorded neurons responded to the stimulation of either the median or tibial nerve, while only 6% responded to the stimulation of both nerves. The vast majority of these pallidal neurons displayed monophasic excitation or monophasic inhibition. The latency of the excitation was shorter than that of the inhibition. In each pallidal segment, the neurons responding to the median nerve stimulation (representing the forelimb) tended to be located ventral to those responding to the tibial nerve stimulation (representing the hindlimb). The present results indicate that the somatotopical arrangement in the globus pallidus can be outlined based on the neuronal responses to peripheral nerve stimulation.

Animals↗

PubMed2003

Glutamatergic propagation of GABAergic seizure-like afterdischarge in the hippocampus in vitro.

Previous investigations have suggested that GABA may act actively as an excitatory mediator in the generation of seizure-like (ictal) or interictal epileptiform activity in several experimental models of temporal lobe epilepsy. However, it remains to be known whether or not such GABAergic excitation may participate in seizure propagation into neighboring cortical regions. In our in vitro study using mature rat hippocampal slices, we examined the cellular mechanism underlying synchronous propagation of seizure-like afterdischarge in the CA1 region, which is driven by depolarizing GABAergic transmission, into the adjacent subiculum region. Tetanically induced seizure-like afterdischarge was always preceded by a GABAergic, slow posttetanic depolarization in the pyramidal cells of the original seizure-generating region. In contrast, the slow posttetanic depolarization was no longer observed in the subicular pyramidal cells when the afterdischarge was induced in the CA1 region. Surgical cutting of axonal pathways through the stratum oriens and the alveus between the CA1 and the subiculum region abolished the CA1-generated afterdischarge in the subicular pyramidal cells. Intracellular loading of fluoride ions, a GABAA receptor blocker, into single subicular pyramidal cells had no inhibitory effect on the CA1-generated afterdischarge in the pyramidal cells. Furthermore, the CA1-generated afterdischarge in the subicular pyramidal cells was largely depressed by local application of glutamate receptor antagonists to the subiculum region during afterdischarge generation. The present results indicate that the excitatory GABAergic generation of seizure-like activity seems to be restricted to epileptogenic foci of origin in the seizure-like epilepsy model in vitro.

Animals↗

PubMed2002

Two-state membrane potential transitions of striatal spiny neurons as evidenced by numerical simulations and electrophysiological recordings in awake monkeys.

Spontaneous membrane potential fluctuations of striatal spiny projection neurons play a crucial role in their spike generation. Previous intracellular recording studies in anesthetized rats have shown that the membrane potential of striatal spiny neurons shifts between the depolarized "up" state and the hyperpolarized "down" state. Here we report evidence for the occurrence of such two-state membrane potential transitions by numerical simulations and electrophysiological recordings in awake monkeys. Data from our simulations of a striatal spiny neuron model demonstrated that spike latency histograms of the model neuron displayed two separate (i.e., early and late) peaks in response to excitatory cortical input, corresponding to neuronal activity in the up or down state, respectively. Then, we addressed experimentally whether the latency distribution of cortically induced spike firing of striatal spiny neurons might show dual peaks. Striatal neuron activity was extracellularly recorded in response to electrical stimulation in the two cortical motor-related areas, the primary motor cortex and the supplementary motor area, of awake monkeys. Analysis of spike latency histograms has defined that striatal spiny neurons typically exhibit two temporally distinct peaks, as obtained by the numerical simulations. Thus, the membrane potential shifts between the up and down states appear to occur in striatal spiny neurons of the behaving animal.

Animals↗

PubMed2002

Noninvasive identification of myocardial sympathetic and metabolic abnormalities in a patient with restrictive cardiomyopathy--in comparison with perfusion imaging.

A 42-year-old man had the insidious onset of heart failure, and was diagnosed as having restrictive cardiomyopathy. Doppler echocardiography study showed short deceleration time of the E wave and short isovolumic relaxation time on transmitral Doppler flow. He underwent Tl-201, I-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and I-123-metaiodobenzylguanidine (MIBG) cardiac scintigraphy. Tl-201 studies showed normal uptake in the left ventricle indicating normal blood perfusion. I-123 BMIPP and I-123 MIBG showed reduced uptake in the inferior segment of the myocardium, indicating impairment of fatty acid metabolism and sympathetic abnormalities.

3-Iodobenzylguanidine↗