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Katsuyuki Kaneda

Publications and source records attributed to Katsuyuki Kaneda.

8 recordsLinked to original sources

Repetitive activation of glutamatergic inputs evokes a long-lasting excitation in rat globus pallidus neurons in vitro.

External globus pallidus (GPe) neurons express abundant metabotropic glutamate receptor 1 (mGluR1) in their somata and dendrites and receive glutamatergic inputs mainly from the subthalamic nucleus. We investigated whether synaptically released glutamate could activate mGluR1s using whole cell and cell-attached recordings in rat brain slice preparations. Repetitive internal capsule stimulation evoked EPSPs followed by a slow depolarizing response (sDEPO) lasting 10-20 s. Bath application of both GABA(A) and GABA(B) receptor antagonists increased the amplitude of sDEPOs. A mixture of AMPA/kainate and N-methyl-d-aspartate receptor antagonists did not alter sDEPOs. The induction of sDEPOs was only partially mediated by mGluR1 because mGluR1 antagonists reduced but failed to completely block the responses. Voltage-clamp recordings revealed that slow inward currents sensitive to mGluR1 antagonist were larger at -60 than at -100 mV, whereas the currents insensitive to mGluR1 antagonist were larger at -100 than at -60 mV. In cell-attached recordings, repetitive internal capsule stimulation evoked long-lasting excitations in GPe neurons, which were also partially suppressed by mGluR1 antagonists. Application of a glutamate uptake inhibitor or an mGluR1 agonist significantly increased the spontaneous firing rate but decreased the excitations to repetitive stimulation. These results suggest that synaptically released glutamate can activate mGluR1, contributing to the induction of long-lasting excitation in GPe neurons and that background mGluR1 activation suppresses the slow mGluR1 responses. Thus mGluR1 may play important roles in the control of GPe neuronal activity.

Animals↗

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↗

Synaptically released GABA activates both pre- and postsynaptic GABA(B) receptors in the rat globus pallidus.

The globus pallidus (GP) contains abundant GABAergic synapses and GABA(B) receptors. To investigate whether synaptically released GABA can activate pre- and postsynaptic GABA(B) receptors in the GP, physiological recordings were performed using rat brain slice preparations. Cell-attached recordings from GABA(A) antagonist-treated preparations revealed that repetitive local stimulation induced a GABA(B) antagonist-sensitive pause in spontaneous firings of GP neurons. Whole cell recordings revealed that the repetitive stimulation evoked fast excitatory postsynaptic potentials followed by a slow inhibitory postsynaptic potential (IPSP) in GP neurons. The slow IPSP was insensitive to a GABA(A) receptor antagonist, increased in amplitude with the application of ionotropic glutamate receptor antagonists, and was suppressed by the GABA(B) antagonist CGP55845. The reversal potential of the slow IPSP was close to the potassium equilibrium potential. These results suggest that synaptically released GABA activated postsynaptic GABA(B) receptors and induced the pause and the slow IPSP. On the other hand, in the neurons that were treated to block postsynaptic GABA(B) responses, CGP55845 increased the amplitudes of repetitive local stimulation-induced GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) but not the ionotropic glutamate-mediated excitatory postsynaptic currents. Moreover, the GABA(B) receptor specific agonist baclofen reduced the frequency of miniature IPSCs without altering their amplitude distributions. These results suggest that synaptically released GABA also activated presynaptic GABA(B) autoreceptors, resulting in decreased GABA release in the GP. Together, we infer that both pre- and postsynaptic GABA(B) receptors may play crucial roles in the control of GP neuronal activity.

Animals↗

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↗

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↗

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↗

Differential processing patterns of motor information via striatopallidal and striatonigral projections.

The functional loop linking the frontal lobe and the basal ganglia plays an important role in the control of motor behaviors. To delineate the principal features of motor information processing in the cortico-basal ganglia loop, the present study aimed at investigating how corticostriatal inputs from the primary motor cortex (MI) and the supplementary motor area (SMA) are transposed onto the pallidal complex and the substantia nigra. In macaque monkeys, stimulating electrodes were chronically implanted into identified forelimb representations of the MI and SMA. Subsequently, the distribution of neurons exhibiting orthodromic responses was examined in the caudal putamen to demarcate striatal zones receiving inputs separately or confluently from the MI and SMA. Finally, anterograde double labeling was performed by paired injections of tracers into two of three identified zones: the MI-recipient zone, SMA-recipient zone, and the convergent zone. Data have revealed that inputs from the MI-recipient and SMA-recipient striatal zones were substantially segregated in the pallidal complex and that those from the convergent zone were distributed to fill in blanks made by terminal bands derived from the MI and SMA. On the other hand, striatonigral inputs from the SMA-recipient and convergent zones of the putamen largely overlapped, while the input from the MI-recipient zone was minimal. The present results clearly indicate that the mode to process corticostriatal motor information through the striatopallidal and striatonigral projections is target-dependent, such that the parallel versus convergent rules govern the arrangement of striatopallidal or striatonigral inputs, respectively.

Afferent Pathways↗

Organization of corticostriatal motor inputs in monkey putamen.

To analyze the organization of corticostriatal motor inputs, we examined the neuronal responses in the putamen (Put) to stimulation in the primary motor cortex (MI) and the supplementary motor area (SMA). Stimulating electrodes were chronically implanted in the distal and proximal parts of the forelimb representation of the MI and in the forelimb representation of the SMA in Japanese monkeys (Macaca fuscata). Stimulation in the MI and SMA evoked orthodromic spike discharges in both phasically active and tonically active Put neurons. The latency of excitation evoked by MI stimulation was shorter than that of excitation evoked by SMA stimulation. Neurons responding exclusively to MI stimulation (MI-recipient neurons) and those responding exclusively to SMA stimulation (SMA-recipient neurons) were distributed predominantly in the ventrolateral and dorsomedial portion of the caudal aspect of the Put, respectively. About 20% of the recorded neurons responded concurrently to stimulation in both the MI and SMA (MI + SMA-recipient neurons). These neurons were located in the intermediate zone between the MI- and SMA-recipient zones. More than half of the Put neurons responded to sensorimotor stimulation. Movements of the forelimb were readily elicited by microstimulation in the MI-recipient zone, less frequently in the MI + SMA-recipient zone, and rarely in the SMA-recipient zone. More detailed analysis of the somatotopic arrangement based on cortical inputs, sensorimotor responses, and microstimulation-evoked movements revealed that within the MI- and MI + SMA-recipient zones of the Put, neurons representing the distal part of the forelimb were located more ventrally than those representing the proximal part. No such somatotopy was clearly detected in the SMA-recipient zone. The present results indicate that corticostriatal inputs from the forelimb regions of the MI and SMA are largely segregated. On the other hand, convergent inputs from the MI and SMA were noted on single neurons located at the junction between the two input zones. In addition, the corticostriatal inputs from the forelimb region of the MI exhibited a distal to proximal somatotopic organization along the ventrodorsal axis of the Put.

Action Potentials↗