Papers by Tetsuo Yamamori
Nature, 2012
It is generally accepted that the direct connection from the motor cortex to spinal motor neurons... more It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates 1-3 . However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs) 4-6 , which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex-PN-motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.
The neocortex consists of histochemically, connectionally, and functionally distinguishable areas... more The neocortex consists of histochemically, connectionally, and functionally distinguishable areas. Recently, molecular biological techniques have enabled us to find rare types of genes expressed in specific neocortical areas. We previously reported occ1 gene as preferentially expressed in the primary visual cortex (V1), using the differential display method. Here, by differential display, we found selective and strong expression of the serum
occ1 is a gene whose expression is particularly abundant in neurons in the macaque primary visual... more occ1 is a gene whose expression is particularly abundant in neurons in the macaque primary visual cortex (V1). In the present study, we report that the expression of occ1 mRNA in the macaque neocortex can be classified into two modes. The first mode is associated with excitatory neurons distributed in the major thalamocortical recipient layers that exhibit strong cytochrome oxidase
Frontiers in cell and developmental biology, 2015
We previously reported the different motor abilities of D1R knockout (KO), D2R KO and wild-type (... more We previously reported the different motor abilities of D1R knockout (KO), D2R KO and wild-type (WT) mice. To understand the interaction between the cerebellum and the striatal direct and indirect pathways, we examined the expression patterns of immediate early genes (IEG) in the cerebellum of these three genotypes of mice. In the WT naive mice, there was little IEG expression. However, we observed a robust expression of c-fos mRNA in the vermis and hemisphere after running rota-rod tasks. In the vermis, c-fos was expressed throughout the lobules except lobule 7, and also in crus 1 of the ansiform lobule (Crus1), copula of the pyramis (Cop) and most significantly in the flocculus in the hemisphere. jun-B was much less expressed but more preferentially expressed in Purkinje cells. In addition, we observed significant levels of c-fos and jun-B expressions after handling mice, and after the stationary rota-rod task in naive mice. Surprisingly, we observed significant expression of c-fo...
Neuroscience Research, 2009
Frontiers in integrative neuroscience, 2014
Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impai... more Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous motor activity in the home cage environment for consecutive 5 days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed...
Frontiers in systems neuroscience, 2014
The identity of the claustrum as a part of cerebral cortex, and in particular of the adjacent ins... more The identity of the claustrum as a part of cerebral cortex, and in particular of the adjacent insular cortex, has been investigated by connectivity features and patterns of gene expression. In the present paper, we mapped the cortical and claustral expression of several cortical genes in rodent and macaque monkey brains (nurr1, latexin, cux2, and netrinG2) to further assess shared features between cortex and claustrum. In mice, these genes were densely expressed in the claustrum, but very sparsely in the cortex and not present in the striatum. To test whether the cortical vs. claustral cell types can be distinguished by co-expression of these genes, we performed a panel of double ISH in mouse and macaque brain. NetrinG2 and nurr1 genes were co-expressed across entire cortex and claustrum, but cux2 and nurr1 were co-expressed only in the insular cortex and claustrum. Latexin was expressed, in the macaque, only in the claustrum. The nurr1 (+) claustral neurons expressed VGluT1, a mark...
Frontiers in neural circuits, 2014
To better understand serotonin function in the primate brain, we examined the mRNA expression pat... more To better understand serotonin function in the primate brain, we examined the mRNA expression patterns of all the 13 members of the serotonin receptor (5HTR) family, by in situ hybridization (ISH) and the distribution of serotonergic terminations by serotonin transporter (SERT) protein immunohistochemical analysis. Ten of the 13 5HTRs showed significant mRNA expressions in the marmoset brain. Our study shows several new features of the organization of serotonergic systems in the marmoset brain. (1) The thalamus expressed only a limited number of receptor subtypes compared with the cortex, hippocampus, and other subcortical regions. (2) In the cortex, there are layer-selective and area-selective mRNA expressions of 5HTRs. (3) Highly localized mRNA expressions of 5HT1F and 5HT3A were observed. (4) There was a conspicuous overlap of the mRNA expressions of receptor subtypes known to have somatodendritic localization of receptor proteins with dense serotonergic terminations in the visua...
Single neuron recordings have shown that there are many color-sensitive neurons in the inferior t... more Single neuron recordings have shown that there are many color-sensitive neurons in the inferior temporal (IT) cortex, but it is still unclear how they distribute in this area. We examined color-related responses in broad brain area, including the IT cortex, by using fMRI in the alert macaque monkey. We measured the BOLD responses to chromatic stimuli (colored gratings and Mondrian-like patterns) and achromatic stimluli (same patterns without color) while the monkey was performing a fixation task. Color-biased responses were observed in LGN, V1, V2, V3 and V4. In addition, some color-biased patches were distributed in the IT cortex; around the posterior middle temporal sulcus, in the posterior bank of the superior temporal sulcus and in the anterior middle temporal sulcus. Their positions were partly overlapped with shape-biased patches detected in a separate experiment. Our results support the hypothesis that color-sensitive neurons are concentrated in multiple sub-regions in the IT cortex.
Frontiers in neural circuits, 2014
Here we present a novel tracing technique to stain projection neurons in Golgi-like detail by dou... more Here we present a novel tracing technique to stain projection neurons in Golgi-like detail by double viral infection. We used retrograde lentiviral vectors and adeno-associated viral vectors (AAV) to drive "TET-ON/TET-OFF system" in neurons connecting two regions. Using this method, we successfully labeled the corticothalamic (CT) cells of the mouse somatosensory barrel field (S1BF) and motor cortex (M1) in their entirety. We also labeled contra- and ipsilaterally-projecting corticocortical (CC) cells of M1 by targeting contralateral M1 or ipsilateral S1 for retrograde infection. The strength of this method is that we can observe the morphology of specific projection neuron subtypes en masse. We found that the group of CT cells extends their dendrites and intrinsic axons extensively below but not within the thalamorecipient layer in both S1BF and M1, suggesting that the primary target of this cell type is not layer 4. We also found that both ipsi- and contralateral targeti...
Neuroscience research, Jan 18, 2014
Here we investigated the transduction characteristics of adeno-associated viral vector (AAV) sero... more Here we investigated the transduction characteristics of adeno-associated viral vector (AAV) serotypes 1, 2, 5, 8 and 9 in the marmoset cerebral cortex. Using three constructs that each has hrGFP under ubiquitous (CMV), or neuron-specific (CaMKII and Synapsin I (SynI)) promoters, we investigated (1) the extent of viral spread, (2) cell type tropism, and (3) neuronal transduction efficiency of each serotype. AAV2 was clearly distinct from other serotypes in small spreading and neuronal tropism. We did not observe significant differences in viral spread among other serotypes. Regarding the cell tropism, AAV1, 5, 8 and 9 exhibited mostly glial expression for CMV construct. However, when the CaMKII construct was tested, cortical neurons were efficiently transduced (>∼70% in layer 3) by all serotypes, suggesting that glial expression obscured neuronal expression for CMV construct. For both SynI and CaMKII constructs, we observed generally high-level expression in large pyramidal cells...
Neuroscience Research, 2007
Single neuron recordings have shown that there are many color-sensitive neurons in the inferior t... more Single neuron recordings have shown that there are many color-sensitive neurons in the inferior temporal (IT) cortex, but it is still unclear how they distribute in this area. We examined color-related responses in broad brain area, including the IT cortex, by using fMRI in the alert macaque monkey. We measured the BOLD responses to chromatic stimuli (colored gratings and Mondrian-like patterns) and achromatic stimluli (same patterns without color) while the monkey was performing a fixation task. Color-biased responses were observed in LGN, V1, V2, V3 and V4. In addition, some color-biased patches were distributed in the IT cortex; around the posterior middle temporal sulcus, in the posterior bank of the superior temporal sulcus and in the anterior middle temporal sulcus. Their positions were partly overlapped with shape-biased patches detected in a separate experiment. Our results support the hypothesis that color-sensitive neurons are concentrated in multiple sub-regions in the IT cortex.
Neuroscience Research, 2009
lation were recorded from the first dorsal interosseous muscle during observation of the action. ... more lation were recorded from the first dorsal interosseous muscle during observation of the action. The MEP amplitudes gradually increased with the number of execution of the same action. However, MEP amplitudes did not changed when the participants only repeated observation of the pinching action or the participants alternately repeated the observation of the pinching action and execution of the abduction of the index finger. These findings suggest that enhancement of cotricospinal excitability is depended on the execution of action with the same manner to the observed action.
Neuroscience, 2008
Recent studies reveal that multisensory convergence can occur in early sensory cortical areas. Ho... more Recent studies reveal that multisensory convergence can occur in early sensory cortical areas. However, the behavioral importance of the multisensory integration in such early cortical areas is unknown. Here, we used c-Fos immunohistochemistry to explore neuronal populations specifically activated during the facilitation of reaction time induced by the temporally congruent audiovisual stimuli in rats. Our newly developed analytical method for c-Fos mapping revealed a pronounced up-regulation of c-Fos expression particularly in layer 4 of the lateral secondary visual area (V2L). A local injection of a GABA A receptor agonist, muscimol, into V2L completely suppressed the audiovisual facilitation of reaction time without affecting responses to unimodal stimuli. Such a selective suppression was not found following the injection of muscimol into the primary auditory and visual areas. To examine whether or not the rats might have shown the facilitated responses because of increment of stimulus intensity caused by the two modal stimuli, the behavioral facilitation induced by the high-intensity unimodal stimuli was tested by the injection of muscimol into V2L, which turned out not to affect the facilitation. These results suggest that V2L, an early visual area, is critically involved in the multisensory facilitation of reaction time induced by the combination of auditory and visual stimuli.
Neural Networks, 2007
Brains are complex networks. Previously, we revealed that specific connected structures are eithe... more Brains are complex networks. Previously, we revealed that specific connected structures are either significantly abundant or rare in cortical networks. However, it remains unknown whether systems from other disciplines have similar architectures to brains. By applying networktheoretical methods, here we show topological similarities between brain and social networks. We found that the statistical relevance of specific tied structures differs between social "friendship" and "disliking" networks, suggesting relation-type-specific topology of social networks. Surprisingly, overrepresented connected structures in brain networks are more similar to those in the friendship networks than to those in other networks. We found that balanced and imbalanced reciprocal connections between nodes are significantly abundant and rare, respectively, whereas these results are unpredictable by simply counting mutual connections. We interpret these results as evidence of positive selection of balanced mutuality between nodes. These results also imply the existence of underlying common principles behind the organization of brain and social networks.
Journal of Neurochemistry, 2001
We applied a differential display PCR technique to isolate molecules that are area-speci®c in exp... more We applied a differential display PCR technique to isolate molecules that are area-speci®c in expression in the primate neocortex, and found that growth/differentiation factor 7 (GDF7), a member of the bone morphogenetic protein (BMP)/transforming growth factor (TGF) beta super-family, is preferentially expressed in the primary motor area of African green monkeys (Cercopithecus aethiops). We proved that GDF7 is 10 times more abundant in the motor cortex than in the visual cortex by northern blotting and quantitative RT-PCR. When we examined the neocortex of closely related rhesus monkeys (Macaca mulatta), GDF7 was also most abundant in the motor cortex, although the regional difference was reduced to 3-fold. This differential expression pattern was observed in both newborn and infant rhesus monkeys. We found that several type I/II receptors of BMP, candidates of the receptors for GDF7, are uniformly expressed in the mature neocortex. The unique expression pattern of GDF7 suggests that it may play an active role in the motor area of the primate neocortex.
The Journal of Comparative Neurology, 2012
Gene markers are useful tools to identify cell types for fine mapping of neuronal circuits. Here ... more Gene markers are useful tools to identify cell types for fine mapping of neuronal circuits. Here we report areaspecific sublamina structure of the rat cerebral cortex using cholecystokinin (cck) and purkinje cell protein4 (pcp4) mRNAs as the markers for excitatory neuron subtypes in layers 5 and 6. We found a segregated expression, especially pronounced in layer 6, where corticothalamic and corticocortical projecting neurons reside. To examine the relationship between gene expression and projection target, we injected retrograde tracers into several thalamic subnuclei, ventral posterior (VP), posterior (PO), mediodorsal (MD), medial and lateral geniculate nuclei (MGN and LGN); as well as into two cortical areas (M1 and V1). This combination of tracer-in situ hybridization (ISH) experiments revealed that corticocortical neurons predominantly express cck and corticothalamic neurons predominantly
Journal of Chemical Neuroanatomy, 2008
occ1/Follistatin-related protein (Frp) is strongly expressed in the primary visual cortex (V1) of... more occ1/Follistatin-related protein (Frp) is strongly expressed in the primary visual cortex (V1) of macaque monkeys, and its expression is strongly down-regulated by intraocular tetrodotoxin (TTX) injection. The pronounced area selectivity of occ1/Frp mRNA expression occurs in macaques and marmosets, but not in mice, rabbits and ferrets, suggesting that occ1/Frp is an important clue to the evolution of the primate cerebral cortex. To further determine species differences, we examined the sensory-input dependency of occ1/Frp mRNA expression in mice in comparison with macaque V1. In macaque V1, occ1/Frp mRNA expression level significantly decreased with even 1-day monocular deprivation (MD) by TTX injection. In contrast to that in macaques, however, the occ1/Frp mRNA expression in the visual cortex in mice was not down-regulated by 1-to 7day MD by TTX injection. Similarly, MD had no effect on occ1/Frp mRNA expression level in the dorsal lateral geniculate nucleus of mice. In addition, the extirpation of the cochlear or olfactory epithelium had no effect on occ1/Frp mRNA expression in either the cochlear nucleus or the olfactory bulb in mice. Thus, occ1/Frp mRNA expression is independent of sensory-input in mice. The results suggest that activity-dependent occ1/Frp mRNA expression is not common between mice and monkeys, and that primate V1 has acquired a unique gene regulatory mechanism that enables a rapid response to environmental changes. The characteristic feature of the activity dependency of occ1/Frp mRNA expression is discussed, in comparison with that of the expression of the immediate-early genes, c-fos and zif268. #
Journal of Biological Chemistry, 2004
Syntaxin 1C is an alternative splice variant lacking the transmembrane domain of HPC-1/syntaxin 1... more Syntaxin 1C is an alternative splice variant lacking the transmembrane domain of HPC-1/syntaxin 1A. We found previously that syntaxin 1C is expressed as a soluble protein in human astroglioma (T98G) cells, and syntaxin 1C expression is enhanced by stimulation with phorbol 12-myristate 13-acetate (PMA). However, the physiological function of syntaxin 1C is not known. In this study, we examined the relationship between syntaxin 1C and glucose transport. First, we discovered that glucose transporter-1 (GLUT-1) was the primary isoform in T98G cells. Second, we demonstrated that glucose uptake in T98G cells was suppressed following an increase in endogenous syntaxin 1C after stimulation with PMA, which did not alter the expression levels of other plasma membrane syntaxins. We further examined glucose uptake and intracellular localization of GLUT-1 in cells that overexpressed exogenous syntaxin 1C; glucose uptake via GLUT-1 was inhibited without affecting sodium-dependent glucose transport. The value of V max for the dose-dependent uptake of glucose was reduced in syntaxin 1C-expressing cells, whereas there was no change in K m . Immunofluorescence studies revealed a reduction in the amount of GLUT-1 in the plasma membrane in cells that expressed syntaxin 1C. Based on these results, we postulate that syntaxin 1C regulates glucose transport in astroglioma cells by changing the intracellular trafficking of GLUT-1. This is the first report to indicate that a syntaxin isoform that lacks a transmembrane domain can regulate the intracellular transport of a plasma membrane protein.
PloS one, 2011
Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. ... more Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement ...
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Papers by Tetsuo Yamamori