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Timing of neurogenesis is correlated with connectivity in locomotor circuits
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Abstracts / Neuroscience Research 71S (2011) e46–e107
These results suggest that the PNs play a crucial role in the control of forelimb movements in the normal condition. Our result also revealed new technical possibility to study functions of neural networks in the primate central nervous system by the pathway-specific and reversible blockade method. Research fund: Strategic Research Program for Brain Sciences. doi:10.1016/j.neures.2011.07.426
O4-H-1-3 Three dimensional distribution of distinct neuronal activity in the periarcuate cortex for reaching by eyes and/or hand Kiyoshi Kurata Dept. Physiol., Hirosaki Grad. Sch. of Med., Hirosaki, Japan In reaching toward an object, human and nonhuman primates execute coordinated hand and eye movements. To seek brain mechanisms responsible for such movements, it is essential to study how and where the coordinated movements are programmed and specialized to execute the eye and hand movements. We focused on the periarcuate cortex including the ventral and dorsal premotor cortex (PMv and PMd, respectively) and the frontal eye field (FEF), and applied two types of instructions, one for an effecter and another for target location, during a preparation period before movement. The monkeys moved a hand held cursor with their right hand on a 45 cm × 30 cm digitizing tablet whose positions and visual cues were displayed on an LCD. We also monitored eye movements using an infrared oculometer. Within a central holding zone for hand movements, a fixation spot for eyes was presented. After 0.6 s holding period, the first instruction signal (IS) for either an effecter (eye, hand, or both) or a target was presented. Further after 0.6 s, the second IS for an effecter or a target was presented. Orders for the two types of ISs were randomized. After the second preparation period, the central spot turned to blue to initiate the instructed movements. If the monkey correctly reached the target, a drop of juice was delivered as a reward. We created three and two dimensional maps of distinct neuronal activities associated with reaching movements by eyes and/or hand around the periarcuate cortex. According to the maps, we suggest that the rostral and caudal FEF play differential roles in saccade initiation and post-saccadic fixation, respectively, whereas the PMv and PMd is more specialized for hand movement preparation and execution. It should be noted that the cortex at the fundus of the arcuate sulcus adjacent to the FEF, PMd, and PMv contains a variety of neuronal activities, possibly contributing to integrating information for coordinated eye–hand movements. Research fund: KAKENHI 22500348. doi:10.1016/j.neures.2011.07.427
O4-H-1-4 Disturbance of voluntary stop in finger reaching task caused by transcranial magnetic stimulation of primary motor cortex Osamu Hiwaki , Naoyuki Ishimaru, Hiroshi Fukuda Grad. Sch. of Info. Sci., Hiroshima City Univ., Hiroshima, Japan Flexible motor acts can be achieved with inhibitory control of voluntary movement. The stop signal task (SST) has been used to investigate the motor response inhibition. In the SST, the stop signal is indicated for subjects to countermand the movement after the go signal. In practice, stopping the movement becomes more difficult as the delay between go and stop signals is extended. However, the neural mechanism underlying the countermanding of reaching movements has not been explored. Studies on the use of transcranial magnetic stimulation (TMS) in upper limb movement control indicated the inhibitory effect of TMS on the primary motor cortex (M1) neurons responsible for execution of movements. In the present report, we investigated the nature of the reaching finger movement after the stop signal accompanied with the TMS of M1 in order to elucidate the temporal function of M1 for the inhibitory control of the voluntary finger movement. The go-stop task of the index finger reaching movement, which consisted of a random mix of the TMS task and the no-TMS task with various stop signal delay (SSD) ranged from 0 to 450 ms in intervals of 50 ms, was performed. In the no-TMS task: the task with the stop signal without the TMS, the finger movement was able be stopped prior to the target when the SSD was shorter than 250 ms. However, in the TMS task: the task with the TMS at the moment of the stop signal, the distance and velocity of the finger movement were significantly greater than those in the no-TMS task when the SSD was shorter than 250 ms. The results indicate that the TMS of the M1 disturbs the inhibitory function of the M1 independently from the pre-programmed voluntary movement.
Research fund: KAKENHI (C) 20560400 from the Ministry of Education, Science, Sports and Culture of Japan. doi:10.1016/j.neures.2011.07.428
O4-H-2-1 Identification of segmentally-arrayed interneurons that regulate larval locomotion in Drosophila Hiroshi Kohsaka 1 , Etsuko Takasu 1 , Akinao Nose 1,2 1
Dept. of Physics, Grad. Sch. of Sci., Univ. of Tokyo, Tokyo, Japan 2 Dept. of Complexity Sci. and Eng., Grad. Sch. of Frontier Science, Univ. of Tokyo, Chiba, Japan
Spatio-temporal activity of neural network underlies all animal behavior. For example, axial locomotion, such as swimming and crawling, is created by sequential activation of arrayed motor neurons along the length of the spinal cord (or the nerve cord in invertebrate). The spatio-temporal activity of motor neurons is in part controlled by interneurons (INs) in the network. While some INs involved in axial locomotion have been identified, their function in ongoing behavior in vivo has not been fully understood. As a model system of locomotion, we use Drosophila larval crawling behavior, which is a propagation of local muscle contraction from posterior to anterior segment. In this study, we report identification and characterization of a genetically-tractable population of INs involved in larval locomotion. We monitored activities of different neuronal populations by calcium imaging with GCaMP, and identified a segmentally-arrayed neural population which exhibit propagation of neural activity along the nerve cord in dissected larvae. Simultaneous imaging of muscle contraction and neural activity showed that the propagation of the neural activity was coincident with the peristalsis-like larval motion. Anatomical studies, including GRASP (GFP Reconstitution Across Synaptic Partners), revealed that these neurons mainly consist of glutamatergic premotor INs. By single cell analysis, we found that these INs are local neurons, which extend neurites within a few segments. Silencing these neurons using temperature sensitive dynamin reduces the speed of the propagation of muscular contraction in the peristaltic locomotion. These results suggest that the segmentally-aligned local INs regulate adequate propagation of neural activity responsible for axial locomotion. Research fund: KAKENHI (19300107, 21700344, 22115001). doi:10.1016/j.neures.2011.07.429
O4-H-2-2 Timing of neurogenesis is correlated with connectivity in locomotor circuits Minoru Koyama , Joseph R. Fetcho Dept. of Neurobiol. and Behav., Cornell Univ., Ithaca, NY, USA Timing of neurogenesis predicts the recruitment pattern of neurons in locomotor circuits in the spinal cord and hindbrain of larval zebrafish: older neurons are active during fast movements while younger ones are active in slow ones. We tested the hypothesis that connectivity from hindbrain reticulospinal (RS) neurons to spinal cord neurons is also correlated with their differentiation time. We first focused on the Mauthner (M) cells, the oldest RS neurons that are only active during fast escape movements. In paired whole-cell recordings we found that M cells connected with primary motoneurons (PMNs, n = 15) and dorsal circumferential descending interneurons (dCiDs, n = 6), both older spinal neurons only active during fast movements. Patch recordings from the MiV1 neurons, some of the youngest RS neurons, revealed that ventral MiV1 neurons are rhythmically active during slow swimming, while dorsal MiV1s are only active during fast/strong movements (n = 15). We tested whether this difference correlates with their time of differentiation by using photoconversion in an Alx:Kaede transgenic line (24–48 hpf; n > 5 for each time point) and found that the dorsal MiV1 neurons are older than the ventral ones. Single cell electroporation of MiV1 neurons (n = 16) showed that the dorsal MiV1 neurons branched extensively near the somata of PMNs and secondary motoneurons (SMNs), while the ventral MiV1 neurons had less extensive branching near the somata of MCoDs, spinal interneurons that are only active in slow swimming. The connections from ventral MiV1 neurons to MCoDs were confirmed by paired whole-cell recordings (n = 6). Thus, older fast movement, hindbrain neurons connect to older fast spinal neurons, and younger, slow hindbrain neurons connect to younger, slow spinal interneurons. These results support the hypothesis that timing of neurogenesis may be a determinant of connectivity in locomotor circuits. Research fund: NINDS NS26539. doi:10.1016/j.neures.2011.07.430
Abstracts / Neuroscience Research 71S (2011) e46–e107
These results suggest that the PNs play a crucial role in the control of forelimb movements in the normal condition. Our result also revealed new technical possibility to study functions of neural networks in the primate central nervous system by the pathway-specific and reversible blockade method. Research fund: Strategic Research Program for Brain Sciences. doi:10.1016/j.neures.2011.07.426
O4-H-1-3 Three dimensional distribution of distinct neuronal activity in the periarcuate cortex for reaching by eyes and/or hand Kiyoshi Kurata Dept. Physiol., Hirosaki Grad. Sch. of Med., Hirosaki, Japan In reaching toward an object, human and nonhuman primates execute coordinated hand and eye movements. To seek brain mechanisms responsible for such movements, it is essential to study how and where the coordinated movements are programmed and specialized to execute the eye and hand movements. We focused on the periarcuate cortex including the ventral and dorsal premotor cortex (PMv and PMd, respectively) and the frontal eye field (FEF), and applied two types of instructions, one for an effecter and another for target location, during a preparation period before movement. The monkeys moved a hand held cursor with their right hand on a 45 cm × 30 cm digitizing tablet whose positions and visual cues were displayed on an LCD. We also monitored eye movements using an infrared oculometer. Within a central holding zone for hand movements, a fixation spot for eyes was presented. After 0.6 s holding period, the first instruction signal (IS) for either an effecter (eye, hand, or both) or a target was presented. Further after 0.6 s, the second IS for an effecter or a target was presented. Orders for the two types of ISs were randomized. After the second preparation period, the central spot turned to blue to initiate the instructed movements. If the monkey correctly reached the target, a drop of juice was delivered as a reward. We created three and two dimensional maps of distinct neuronal activities associated with reaching movements by eyes and/or hand around the periarcuate cortex. According to the maps, we suggest that the rostral and caudal FEF play differential roles in saccade initiation and post-saccadic fixation, respectively, whereas the PMv and PMd is more specialized for hand movement preparation and execution. It should be noted that the cortex at the fundus of the arcuate sulcus adjacent to the FEF, PMd, and PMv contains a variety of neuronal activities, possibly contributing to integrating information for coordinated eye–hand movements. Research fund: KAKENHI 22500348. doi:10.1016/j.neures.2011.07.427
O4-H-1-4 Disturbance of voluntary stop in finger reaching task caused by transcranial magnetic stimulation of primary motor cortex Osamu Hiwaki , Naoyuki Ishimaru, Hiroshi Fukuda Grad. Sch. of Info. Sci., Hiroshima City Univ., Hiroshima, Japan Flexible motor acts can be achieved with inhibitory control of voluntary movement. The stop signal task (SST) has been used to investigate the motor response inhibition. In the SST, the stop signal is indicated for subjects to countermand the movement after the go signal. In practice, stopping the movement becomes more difficult as the delay between go and stop signals is extended. However, the neural mechanism underlying the countermanding of reaching movements has not been explored. Studies on the use of transcranial magnetic stimulation (TMS) in upper limb movement control indicated the inhibitory effect of TMS on the primary motor cortex (M1) neurons responsible for execution of movements. In the present report, we investigated the nature of the reaching finger movement after the stop signal accompanied with the TMS of M1 in order to elucidate the temporal function of M1 for the inhibitory control of the voluntary finger movement. The go-stop task of the index finger reaching movement, which consisted of a random mix of the TMS task and the no-TMS task with various stop signal delay (SSD) ranged from 0 to 450 ms in intervals of 50 ms, was performed. In the no-TMS task: the task with the stop signal without the TMS, the finger movement was able be stopped prior to the target when the SSD was shorter than 250 ms. However, in the TMS task: the task with the TMS at the moment of the stop signal, the distance and velocity of the finger movement were significantly greater than those in the no-TMS task when the SSD was shorter than 250 ms. The results indicate that the TMS of the M1 disturbs the inhibitory function of the M1 independently from the pre-programmed voluntary movement.
Research fund: KAKENHI (C) 20560400 from the Ministry of Education, Science, Sports and Culture of Japan. doi:10.1016/j.neures.2011.07.428
O4-H-2-1 Identification of segmentally-arrayed interneurons that regulate larval locomotion in Drosophila Hiroshi Kohsaka 1 , Etsuko Takasu 1 , Akinao Nose 1,2 1
Dept. of Physics, Grad. Sch. of Sci., Univ. of Tokyo, Tokyo, Japan 2 Dept. of Complexity Sci. and Eng., Grad. Sch. of Frontier Science, Univ. of Tokyo, Chiba, Japan
Spatio-temporal activity of neural network underlies all animal behavior. For example, axial locomotion, such as swimming and crawling, is created by sequential activation of arrayed motor neurons along the length of the spinal cord (or the nerve cord in invertebrate). The spatio-temporal activity of motor neurons is in part controlled by interneurons (INs) in the network. While some INs involved in axial locomotion have been identified, their function in ongoing behavior in vivo has not been fully understood. As a model system of locomotion, we use Drosophila larval crawling behavior, which is a propagation of local muscle contraction from posterior to anterior segment. In this study, we report identification and characterization of a genetically-tractable population of INs involved in larval locomotion. We monitored activities of different neuronal populations by calcium imaging with GCaMP, and identified a segmentally-arrayed neural population which exhibit propagation of neural activity along the nerve cord in dissected larvae. Simultaneous imaging of muscle contraction and neural activity showed that the propagation of the neural activity was coincident with the peristalsis-like larval motion. Anatomical studies, including GRASP (GFP Reconstitution Across Synaptic Partners), revealed that these neurons mainly consist of glutamatergic premotor INs. By single cell analysis, we found that these INs are local neurons, which extend neurites within a few segments. Silencing these neurons using temperature sensitive dynamin reduces the speed of the propagation of muscular contraction in the peristaltic locomotion. These results suggest that the segmentally-aligned local INs regulate adequate propagation of neural activity responsible for axial locomotion. Research fund: KAKENHI (19300107, 21700344, 22115001). doi:10.1016/j.neures.2011.07.429
O4-H-2-2 Timing of neurogenesis is correlated with connectivity in locomotor circuits Minoru Koyama , Joseph R. Fetcho Dept. of Neurobiol. and Behav., Cornell Univ., Ithaca, NY, USA Timing of neurogenesis predicts the recruitment pattern of neurons in locomotor circuits in the spinal cord and hindbrain of larval zebrafish: older neurons are active during fast movements while younger ones are active in slow ones. We tested the hypothesis that connectivity from hindbrain reticulospinal (RS) neurons to spinal cord neurons is also correlated with their differentiation time. We first focused on the Mauthner (M) cells, the oldest RS neurons that are only active during fast escape movements. In paired whole-cell recordings we found that M cells connected with primary motoneurons (PMNs, n = 15) and dorsal circumferential descending interneurons (dCiDs, n = 6), both older spinal neurons only active during fast movements. Patch recordings from the MiV1 neurons, some of the youngest RS neurons, revealed that ventral MiV1 neurons are rhythmically active during slow swimming, while dorsal MiV1s are only active during fast/strong movements (n = 15). We tested whether this difference correlates with their time of differentiation by using photoconversion in an Alx:Kaede transgenic line (24–48 hpf; n > 5 for each time point) and found that the dorsal MiV1 neurons are older than the ventral ones. Single cell electroporation of MiV1 neurons (n = 16) showed that the dorsal MiV1 neurons branched extensively near the somata of PMNs and secondary motoneurons (SMNs), while the ventral MiV1 neurons had less extensive branching near the somata of MCoDs, spinal interneurons that are only active in slow swimming. The connections from ventral MiV1 neurons to MCoDs were confirmed by paired whole-cell recordings (n = 6). Thus, older fast movement, hindbrain neurons connect to older fast spinal neurons, and younger, slow hindbrain neurons connect to younger, slow spinal interneurons. These results support the hypothesis that timing of neurogenesis may be a determinant of connectivity in locomotor circuits. Research fund: NINDS NS26539. doi:10.1016/j.neures.2011.07.430