Biomedical subjects

Hironobu Tokuno

Publications and source records attributed to Hironobu Tokuno.

14 recordsLinked to original sources

PubMed2006

The parafascicular nucleus relays spinal inputs to the striatum: an electron microscope study in the rat.

A disynaptic projection from the spinal cord to the striatum was observed in the rat light and electron microscopically. An anterograde tracer, wheat germ agglutinin conjugated to horseradish peroxidase was injected into the ventral gray matter of the upper cervical spinal cord, and a retrograde tracer, biotinylated dextran amine was injected into the striatum of a rat. Then the parafascicular nucleus was examined. Some anterogradely labeled axon terminals originating in the spinal cord were observed to synapse with retrogradely labeled dendrites of parafascicular nucleus neurons which sent axons to the striatum. We concluded that information from the spinal cord was transmitted to the striatum, being relayed by parafascicular nucleus neurons.

Afferent Pathways↗

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

Post-translational excision of the carboxyl-terminal segment of CaM kinase phosphatase N and its cytosolic occurrence in the brain.

Ca2+/Calmodulin-dependent protein kinase (CaM kinase) phosphatase, occurring in the cytoplasm of all tissues, dephosphorylates and thereby deactivates multifunctional CaM kinases, such as CaM kinases I, II and IV. In contrast, CaM kinase phosphatase N has been reported to occur almost exclusively in the brain and to be localized in the nucleus in the transfected COS-7 cells, as examined immunocytochemically with antibodies against the carboxyl-terminal segment of the enzyme, indicating its involvement in the deactivation of CaM kinase IV. Here, we show that the majority of the naturally occurring CaM kinase phosphatase N in the brain exists not in the intact form of the enzyme (83.4 kDa) but in a form (61.1 kDa) in which the carboxyl-terminal segment containing nuclear localization signals is deleted, and that it is present mostly in the cytoplasm but a little in the nucleus throughout the central nervous system, although occurring mostly in the nucleus in some large neurons. Strong immunostaining of the enzyme was also observed at postsynaptic density. These findings suggest that CaM kinase phosphatase N is involved in the regulation of not only CaM kinase IV but also CaM kinases II and I.

Amino Acid Sequence↗

PubMed2005

Impairment of skilled forelimb use after ablation of striatal interneurons expressing substance P receptors in rats: an analysis using a pasta matrix reaching task.

Local injection of substance P (SP)-saporin can cause selective ablation of striatal interneurons expressing SP receptors (SPR). In this study, we evaluated quantitatively the impairment of skilled forelimb use after unilateral ablation of the striatal interneurons using a pasta matrix reaching task in rats. We found a significant decrease of the number of the pasta pieces (uncooked spaghetti) retrieved using the paw of the experimental side contralateral to the ablation, whereas the number of the pasta pieces retrieved using the paw of the intact side increased significantly. These findings, with our previous reports, suggest that the modulation of the cortico-striato-entopeduncular direct pathway by striatal interneurons is important for maintaining normal basal-ganglia control for skilled forelimb movements.

Animals↗

PubMed2004

Three-dimensional ultrasonography of monkey brain.

Three-dimensional (3D) ultrasonography is new technology based on automatic volume acquisition of ultrasound images, and computer-aided image reconstruction. In the present study, we used a commercially available 3D ultrasonographic instrument for electrophysiological and neuroanatomical experiments in the macaque monkey. 3D reconstruction for multiplanar analysis and surface rendering were useful to observe the microelectrode or microinjection pipette in the cerebral cortex or deep brain structure. The present results indicate that the 3D ultrasonography for monkey brain is a more powerful tool for experiments in vivo than conventional two-dimensional (2D) ultrasonography.

Animals↗

PubMed2003

Cytochrome oxidase activity in the monkey globus pallidus and subthalamic nucleus after ablation of striatal interneurons expressing substance P receptors.

To understand functional roles of striatal interneurons in primate basal ganglia circuitry, we ablated interneurons expressing substance P (SP) receptors (SPR) in the putamen with SP-saporin, a SPR selective neurotoxin. The effect of SP-saporin injection into the putamen was evaluated by examining the loss of cholinergic interneurons and NADPHd-positive (nicotinamide adenine dinucleotide phosphate diaphorase positive) interneurons. We then analyzed regional metabolic changes using cytochrome oxidase (CO) histochemistry. CO activity in some regions of the internal and external segments of the globus pallidus (GP) in the lesioned hemisphere was lower than that in the contralateral or surrounding GP regions. CO activity in the subthalamic nucleus, however, showed no significant change. The present findings suggest that striatopallidal projection neurons exert enhanced inhibitory influence on the GP without modulatory control by the striatal SPR-expressing interneurons.

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

Fluorescence digital photomacrography.

Low-power photographs of brain sections have been needed for neuroanatomical studies. This paper describes a setup for fluorescence digital photomacrography. High-resolution digital images were obtained with commercially available digital cameras combined with an oblique fluorescence illumination and filters for excitation and emission. The image of an entire coronal section of the macaque brain could be taken with a single exposure. The present photographic system would be useful not only for neuroanatomical, but also for histological, embryological or pathological studies that require low-magnification fluorescence images.

Animals↗

PubMed2003

Ablation of striatal interneurons influences activities of entopeduncular neurons.

To characterize modulatory effects of striatal interneurons upon the output nucleus of the basal ganglia, we ablated striatal interneurons that express substance P receptors by using local injection of a selective neurotoxin, substance P-saporin, in rats. We then made extracellular recordings of the activity of entopeduncular neurons and examined their responses to stimulation in the motor cortex. In the interneuron-ablated animals, the spontaneous discharge rate of entopeduncular neurons was significantly decreased, and the proportion of entopeduncular neurons showing responses to cortical stimulation was significantly larger, in comparison with intact animals. It is suggested that striatal interneurons expressing substance P receptors are important for motor control mechanisms mediated by the cortico-basal ganglia pathways.

Action Potentials↗

PubMed2002

Efferent projections from the striatal patch compartment: anterograde degeneration after selective ablation of neurons expressing mu-opioid receptor in rats.

Local injection of mu-opioid receptor specific neurotoxin, dermorphin-saporin, into the striatum resulted in selective degeneration of striatal neurons in the patch compartment. We analyzed subsequent anterograde degeneration of axons and terminals at light and electron microscopic level. Light microscopic examination after silver impregnation method revealed that degenerating axons and terminals arising from the striatal patch compartment were distributed in the globus pallidus, entopeduncular nucleus, and substantia nigra. They were found in both pars reticulata and compacta of the substantia nigra. Electron microscopic examination revealed that the degenerating axon terminals contained large pleomorphic vesicles and formed symmetric synapses on dendrites. The present results suggest that patch neurons expressing mu-opioid receptor send projection fibers to multiple nuclei of the basal ganglia.

Animals↗

PubMed2002

Functional significance of the cortico-subthalamo-pallidal 'hyperdirect' pathway.

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. The cortico-subthalamo-pallidal 'hyperdirect' pathway conveys powerful excitatory effects from the motor-related cortical areas to the globus pallidus, bypassing the striatum, with shorter conduction time than effects conveyed through the striatum. We emphasize the functional significance of the 'hyperdirect' pathway and propose a dynamic 'center-surround model' of basal ganglia function in the control of voluntary limb movements. When a voluntary movement is about to be initiated by cortical mechanisms, a corollary signal conveyed through the cortico-subthalamo-pallidal 'hyperdirect' pathway first inhibits large areas of the thalamus and cerebral cortex that are related to both the selected motor program and other competing programs. Then, another corollary signal through the cortico-striato-pallidal 'direct' pathway disinhibits their targets and releases only the selected motor program. Finally, the third corollary signal possibly through the cortico-striato-external pallido-subthalamo-internal pallidal 'indirect' pathway inhibits their targets extensively. Through this sequential information processing, only the selected motor program is initiated, executed and terminated at the selected timing, whereas other competing programs are canceled.

Animals↗

PubMed2002

An improved method with a long-shanked glass micropipette and ultrasonography for drug injection into deep brain structure of the monkey.

We describe an improved method to inject drug into deep brain structure of the macaque monkey. A Teflon-coated tungsten wire for extracellular recording was passed through a long-shanked (4-5 cm) glass micropipette, which was then attached to a microsyringe with dental impression material. The surface of the micropippete was coated with Teflon to reduce acoustic artifact in ultrasound imaging. Thereby, it was possible to identify the micropipette in the brain with B-mode ultrasonography. Extracellular recording combined with electrical stimulation in the input source of the target nucleus was also helpful to determine the location of the micropipette. Here, we demonstrate injection of a neuronal tracer, wheat germ agglutinin conjugated to horseradish peroxidase, into the medial mammillary nucleus of the Japanese monkey.

Action Potentials↗

PubMed2002

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↗

PubMed2002

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↗