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Expression of Foxp2 in mouse cerebellum changes from a homogeneous to a transversely oriented stripe-like pattern during development from embryo to adult
Abstracts / Neuroscience Research 71S (2011) e46–e107
it could also be applied for the functional electrical stimulation for restoring body movements. Research fund: JST-Presto.
e89
such stimulus-intensity-specific conditioning is equivalent to the endpoint variability suppression of saccades. doi:10.1016/j.neures.2011.07.382
doi:10.1016/j.neures.2011.07.380
O4-C-2-1 Expression of Foxp2 in mouse cerebellum changes from a homogeneous to a transversely oriented stripe-like pattern during development from embryo to adult Hirofumi Fujita , Izumi Sugihara Systems Neurophisiol., Grad. Sch. of Med., Tokyo Med. and Dent. Univ., Tokyo, Japan Purkinje cells (PCs) are heterogeneous in their molecular expression despite their uniform morphological and functional properties. Molecular expression in PCs differs depending on the developmental stage and on the location of PCs in the cerebellum. For example, aldolase C is expressed in a subpopulation of PCs that are arranged in ‘longitudinal’ (=parasagittal) stripes in the adult. Another molecule, calbindin-D28k, is expressed only in a subpopulation of PCs that are clustered in specific locations in embryo, although it is expressed in all PCs, and is hence a molecular marker for PCs, in the adult. FoxP2, a forkhead box transcription factor involved in vocal communication or language, is strongly expressed in PCs as well as in the forebrain. However, developmental and locational changes in its expression in PCs remain unclear. In the present study we examined Foxp2 expression in the mouse cerebellar cortex systematically by immunostaining serial sections from embryonic day 14.5 to adult. Before postnatal day 6 (P6), all PCs were almost uniformly Foxp2positive except for those in the flocculus. After P6, some populations of PCs gradually became Foxp2-negative. As a consequence, the adult cerebellar cortex displays a transverse stripe-like expression pattern. Double immunostaining for Foxp2 and aldolase C revealed little relationship between their expression patterns. Moreover, the Foxp2 expression pattern in the adult cerebellum indicates a new transverse compartmentalization that does not resemble any other molecular expression patterns so far reported. The functional significance of this transverse compartmentalization is not clear, but Foxp2 expression in the adult mouse cerebellum is not likely to be specifically related to vocal communication. On the other hand, Foxp2 may be involved in the general differentiation of PCs in embryo, and can be useful as a molecular marker for developing PCs. Research fund: KAKENHI20300137. doi:10.1016/j.neures.2011.07.381
O4-C-2-2 A unified theory of cerebellar motor learning for saccadic adaptation and eyeblink conditioning Masahiko Fujita Fac. of Sci. and Eng., Hosei Univ., Tokyo, Japan Saccades show endpoint variability even when made repetitively to the same target while random noise in motor commands and visual uncertainty of target localization seem to degrade accuracy. Cerebellar lesioning can greatly increase the endpoint variability of saccades, and also deprive the saccade system of its ability for rapid adaptation with the double-step paradigm. Since motor noise seems to occur in the upper stream during saccade command generation, feedback control may be ineffective in adjusting the trajectory. Furthermore, even if the rapid adaptation could be completed in a single trial, the reduced (or increased) gain would make a saccade more hypometric (or hypermetric) for a subsequent undersized (or oversized) command. Thus, rapid adaptation alone cannot explain the reduction of variability. This severe challenge to the traditional concepts of cerebellar function can be resolved if the cerebellum encodes noisy input variation as an internal differential representation and combines it with a motor performance result. Motor learning derived from such a causal relationship could perform adaptation and also cancel endpoint and trajectory variability. To implement this function, I have proposed a novel preprocessing step performed by a system comprising Golgi and granule cells that endows the cortex with a universal learning ability. This learning ability not only leads to successful simulations of the rapid adaptation and variability suppression of saccades but also to that of classical eyeblink conditionings. This conditioning simulation shows generalization with respect to the frequency and intensity of the conditioning stimulus and also discrimination of the frequency. Here I propose an experiment that predicts an intensity-specific eyeblink conditioning in which a weak tone will evoke eyeblink while a strong tone will not. Theoretically,
O4-C-2-3 Single-neuron tracing study of thalamocortical projections arising from the rat ventral medial nucleus by using viral vectors Eriko Kuramoto 1 , Sachi Ohno 1,2 , Fumino Fujiyama 1,3 , Takahiro Furuta 1 , Tomo Unzai 1 , Hiroyuki Hioki 1 , Yasuhiro Tanaka 1 , Takeshi Kaneko 1 1
Dept. of Morphol. Brain Sci., Grad. Sch. of Med., Kyoto Univ., Kyoto, Japan Dept. Dental Anesthesiology, Grad. Sch. of Med. and Dent., Kagoshima Univ., Kagoshima, Japan 3 JST, CREST 2
The rat motor thalamic nuclei are composed of ventral medial (VM), ventral anterior (VA) and ventral lateral nuclei (VL). The caudodorsal portion of the VA–VL receives glutamatergic afferents from the cerebellum, whereas the VM and rostroventral portion of the VA–VL receive GABAergic afferents from the basal ganglia. Previously we reported that axonal arborization was different between the rostroventral and caudodorsal VA–VL neurons by using single neuron-tracing method with Sindbis viral vector expressing membrane-targeted GFP. In the present study, the axonal arborization of single VM neurons was examined by the same method, and compared with the previous results of VA–VL neurons. When the axons exited from the thalamus, the reconstructed VM neurons always emitted axon collaterals to the thalamic reticular nucleus as VA–VL neurons. The VM neurons formed less axonal arborization in the striatum than rostrovental VA–VL neurons. In the cerebral cortex, the VM neurons sent axon fibers to more widespread cortical areas than VA–VL neurons, projecting to the primary motor, secondary motor, primary somatosensory, orbital, cingulate and insular areas. Of cortical layers, the axon fibers of VM neurons were most abundantly distributed in layer 1 (78.1 ± 5.6%), especially in the superficial part of layer 1. In comparison with the previously reported data of rostroventral (54%) and cuadodorsal VA–VL neurons (5.6%), VM neurons highly preferred layer 1 to other cortical layers. Although both the VM and rostroventral VA–VL have been reported to receive massive afferents mainly from the basal ganglia, the present results indicate that VM neurons more intensely innervate apical dendrites of pyramidal neurons in more widespread frontal/limbic areas than rostroventral VA–VL neurons. This suggests that, of motor thalamic neurons, VM neurons are most specialized to control the gain of widespread pyramidal neurons simultaneously. Research fund: KAKENHI 20020014, 22700367, 22700368, 17022020, 22300113. doi:10.1016/j.neures.2011.07.383
O4-C-2-4 Functional and anatomical network linking the basal ganglia and cerebral cortex: In vivo MRI study Nobukatsu Sawamoto 1 , Takuya Oguri 1,2 , Hayato Tabu 1 , Hidenao Fukuyama 1 1 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan 2 Department of Neurology & Neuroscience, Graduate School of Medical Sciences, Nagoya City University
It has been proposed that the basal ganglia, as components of multiple parallel and segregated circuits, integrate and funnels inputs only from several functionally related cortical areas, and then send back outputs to the cortical areas providing the inputs to the circuit (Alexander et al., 1986). The circuits have been proposed to exist at least five, and the corresponding cortical components are the supplementary motor area (SMA), frontal eye fields (FEF), dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC). We investigated whether the proposed five circuits are parallel and segregated, or not, by examining functional and anatomical connectivity between the cortex and striatum in healthy human brain. Resting-state fMRI, diffusion weighted images (DWI) and T1 image of 20 volunteers were acquired on a 3T. With labels on cortical gyri and sulci generated by FreeSurfer and additional criteria, we created masks on the SMA (Mayka et al., 2006), FEF (Paus, 1996), DLPFC (Rajkowska et al., 1995), OFC (Petrides, 2000) and ACC (Vogt et al., 2003). Taking the preprocessed fMRI data, the major Eigen time series in each mask were identified, and the partial correlation scores were calculated for each voxel in the brain. With the preprocessed DWI data, probabilistic tractography was run from the striatum to each cortical mask. Resting-state fMRI showed that spatially restricted zones in the striatum were specifically correlated with each cortical region
it could also be applied for the functional electrical stimulation for restoring body movements. Research fund: JST-Presto.
e89
such stimulus-intensity-specific conditioning is equivalent to the endpoint variability suppression of saccades. doi:10.1016/j.neures.2011.07.382
doi:10.1016/j.neures.2011.07.380
O4-C-2-1 Expression of Foxp2 in mouse cerebellum changes from a homogeneous to a transversely oriented stripe-like pattern during development from embryo to adult Hirofumi Fujita , Izumi Sugihara Systems Neurophisiol., Grad. Sch. of Med., Tokyo Med. and Dent. Univ., Tokyo, Japan Purkinje cells (PCs) are heterogeneous in their molecular expression despite their uniform morphological and functional properties. Molecular expression in PCs differs depending on the developmental stage and on the location of PCs in the cerebellum. For example, aldolase C is expressed in a subpopulation of PCs that are arranged in ‘longitudinal’ (=parasagittal) stripes in the adult. Another molecule, calbindin-D28k, is expressed only in a subpopulation of PCs that are clustered in specific locations in embryo, although it is expressed in all PCs, and is hence a molecular marker for PCs, in the adult. FoxP2, a forkhead box transcription factor involved in vocal communication or language, is strongly expressed in PCs as well as in the forebrain. However, developmental and locational changes in its expression in PCs remain unclear. In the present study we examined Foxp2 expression in the mouse cerebellar cortex systematically by immunostaining serial sections from embryonic day 14.5 to adult. Before postnatal day 6 (P6), all PCs were almost uniformly Foxp2positive except for those in the flocculus. After P6, some populations of PCs gradually became Foxp2-negative. As a consequence, the adult cerebellar cortex displays a transverse stripe-like expression pattern. Double immunostaining for Foxp2 and aldolase C revealed little relationship between their expression patterns. Moreover, the Foxp2 expression pattern in the adult cerebellum indicates a new transverse compartmentalization that does not resemble any other molecular expression patterns so far reported. The functional significance of this transverse compartmentalization is not clear, but Foxp2 expression in the adult mouse cerebellum is not likely to be specifically related to vocal communication. On the other hand, Foxp2 may be involved in the general differentiation of PCs in embryo, and can be useful as a molecular marker for developing PCs. Research fund: KAKENHI20300137. doi:10.1016/j.neures.2011.07.381
O4-C-2-2 A unified theory of cerebellar motor learning for saccadic adaptation and eyeblink conditioning Masahiko Fujita Fac. of Sci. and Eng., Hosei Univ., Tokyo, Japan Saccades show endpoint variability even when made repetitively to the same target while random noise in motor commands and visual uncertainty of target localization seem to degrade accuracy. Cerebellar lesioning can greatly increase the endpoint variability of saccades, and also deprive the saccade system of its ability for rapid adaptation with the double-step paradigm. Since motor noise seems to occur in the upper stream during saccade command generation, feedback control may be ineffective in adjusting the trajectory. Furthermore, even if the rapid adaptation could be completed in a single trial, the reduced (or increased) gain would make a saccade more hypometric (or hypermetric) for a subsequent undersized (or oversized) command. Thus, rapid adaptation alone cannot explain the reduction of variability. This severe challenge to the traditional concepts of cerebellar function can be resolved if the cerebellum encodes noisy input variation as an internal differential representation and combines it with a motor performance result. Motor learning derived from such a causal relationship could perform adaptation and also cancel endpoint and trajectory variability. To implement this function, I have proposed a novel preprocessing step performed by a system comprising Golgi and granule cells that endows the cortex with a universal learning ability. This learning ability not only leads to successful simulations of the rapid adaptation and variability suppression of saccades but also to that of classical eyeblink conditionings. This conditioning simulation shows generalization with respect to the frequency and intensity of the conditioning stimulus and also discrimination of the frequency. Here I propose an experiment that predicts an intensity-specific eyeblink conditioning in which a weak tone will evoke eyeblink while a strong tone will not. Theoretically,
O4-C-2-3 Single-neuron tracing study of thalamocortical projections arising from the rat ventral medial nucleus by using viral vectors Eriko Kuramoto 1 , Sachi Ohno 1,2 , Fumino Fujiyama 1,3 , Takahiro Furuta 1 , Tomo Unzai 1 , Hiroyuki Hioki 1 , Yasuhiro Tanaka 1 , Takeshi Kaneko 1 1
Dept. of Morphol. Brain Sci., Grad. Sch. of Med., Kyoto Univ., Kyoto, Japan Dept. Dental Anesthesiology, Grad. Sch. of Med. and Dent., Kagoshima Univ., Kagoshima, Japan 3 JST, CREST 2
The rat motor thalamic nuclei are composed of ventral medial (VM), ventral anterior (VA) and ventral lateral nuclei (VL). The caudodorsal portion of the VA–VL receives glutamatergic afferents from the cerebellum, whereas the VM and rostroventral portion of the VA–VL receive GABAergic afferents from the basal ganglia. Previously we reported that axonal arborization was different between the rostroventral and caudodorsal VA–VL neurons by using single neuron-tracing method with Sindbis viral vector expressing membrane-targeted GFP. In the present study, the axonal arborization of single VM neurons was examined by the same method, and compared with the previous results of VA–VL neurons. When the axons exited from the thalamus, the reconstructed VM neurons always emitted axon collaterals to the thalamic reticular nucleus as VA–VL neurons. The VM neurons formed less axonal arborization in the striatum than rostrovental VA–VL neurons. In the cerebral cortex, the VM neurons sent axon fibers to more widespread cortical areas than VA–VL neurons, projecting to the primary motor, secondary motor, primary somatosensory, orbital, cingulate and insular areas. Of cortical layers, the axon fibers of VM neurons were most abundantly distributed in layer 1 (78.1 ± 5.6%), especially in the superficial part of layer 1. In comparison with the previously reported data of rostroventral (54%) and cuadodorsal VA–VL neurons (5.6%), VM neurons highly preferred layer 1 to other cortical layers. Although both the VM and rostroventral VA–VL have been reported to receive massive afferents mainly from the basal ganglia, the present results indicate that VM neurons more intensely innervate apical dendrites of pyramidal neurons in more widespread frontal/limbic areas than rostroventral VA–VL neurons. This suggests that, of motor thalamic neurons, VM neurons are most specialized to control the gain of widespread pyramidal neurons simultaneously. Research fund: KAKENHI 20020014, 22700367, 22700368, 17022020, 22300113. doi:10.1016/j.neures.2011.07.383
O4-C-2-4 Functional and anatomical network linking the basal ganglia and cerebral cortex: In vivo MRI study Nobukatsu Sawamoto 1 , Takuya Oguri 1,2 , Hayato Tabu 1 , Hidenao Fukuyama 1 1 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan 2 Department of Neurology & Neuroscience, Graduate School of Medical Sciences, Nagoya City University
It has been proposed that the basal ganglia, as components of multiple parallel and segregated circuits, integrate and funnels inputs only from several functionally related cortical areas, and then send back outputs to the cortical areas providing the inputs to the circuit (Alexander et al., 1986). The circuits have been proposed to exist at least five, and the corresponding cortical components are the supplementary motor area (SMA), frontal eye fields (FEF), dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC). We investigated whether the proposed five circuits are parallel and segregated, or not, by examining functional and anatomical connectivity between the cortex and striatum in healthy human brain. Resting-state fMRI, diffusion weighted images (DWI) and T1 image of 20 volunteers were acquired on a 3T. With labels on cortical gyri and sulci generated by FreeSurfer and additional criteria, we created masks on the SMA (Mayka et al., 2006), FEF (Paus, 1996), DLPFC (Rajkowska et al., 1995), OFC (Petrides, 2000) and ACC (Vogt et al., 2003). Taking the preprocessed fMRI data, the major Eigen time series in each mask were identified, and the partial correlation scores were calculated for each voxel in the brain. With the preprocessed DWI data, probabilistic tractography was run from the striatum to each cortical mask. Resting-state fMRI showed that spatially restricted zones in the striatum were specifically correlated with each cortical region