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Changes in directional tuning of primate motor cortex cells driving an artificial corticospinal connection
Abstracts / Neuroscience Research 68S (2010) e109–e222
P1-g18 Optogenetically induced suppression of neural activity in the macaque motor cortex Masaharu Kinoshita 1 , Katsuyuki Kaneda 1 , Hironori Kasahara 3 , Nobuhiko Hatanaka 2 , Ryosuke Matsui 3 , Satomi Chiken 2 , Kaoru Isa 1 , Hiroaki Mizukami 4 , Keiya Ozawa 4 , Dai Watanabe 3 , Atsushi Nambu 2 , Tadashi Isa 1 1
Dept. Dev. Physiol., NIPS, Okazaki, Japan 2 System Neurophysiol, NIPS, Okazaki, Japan 3 Lab Neurosci, Grad Sch Biostudies, Kyoto Univ, Kyoto, Japan 4 Div Genetic Therap, Ctr Molecular Medicine, Jichi Medical Univ., Tochigi, Japan The methods to selectively block spiking activities in the central nervous system are the powerful tools for investigating the functions of neural circuits in the brain. Recently, halorhodopsin (NpHR), a light-sensitive chloride pump of Natronomonas pharaonis, was found to be activated by yellow light (∼580nm) and activation of NpHR expressed in neurons led to hyperpolarization effective enough for suppression of the spiking activity. This optogenetic method allows us to recoverable and precise timing control of the selective blockade of spiking activity in the identified neurons. In this study, we tried to express eNpHR, a modified NpHR that contains membrane-trafficking signal sequences, in the hand-region of the primary motor cortex (M1) of macaque monkeys with viral vectors and tested the possibilities of photo-induced blockade of neural activities. In the monkey, neurons in the hand region of M1 send descending commands of finger movements to motor neurons innervating hand muscles. We have introduced eNpHR into the hand region of M1 of macaque monkeys with lentivirus vector with CaMKII␣ promoter to block the activity of cortical neurons involved in the control of hand movements. One month after the injection, we found that spike activity of the M1 neurons, induced by electrical stimulation of the premotor cortex, was successfully suppressed by applying the yellow laser with an optorode, a thin metal electrode combined with an optical fiber. This result will open up a new field of neuroscience research by enabling the neural pathway-specific blockade of signal transmission in macaque monkeys. doi:10.1016/j.neures.2010.07.2233
P1-h01 Changes in directional tuning of primate motor cortex cells driving an artificial corticospinal connection Yukio Nishimura 1,2 , Steve I. Perlmutter 1 , Eberhard E. Fetz 1 1
Department of Physiology & Biophysics and Washington National Primate Research Center, University of Washington, Seattle, Washington, USA 2 PRESTO, Japan Science and Technology Agency, Chiyoda, Tokyo, Japan In primates, corticospinal (CS) connections are essential to control forelimb movements. Patients with damaged CS pathways exhibit severe motor deficits, and might benefit from artificial connections. We investigated effects of introducing novel CS connections in 2 intact monkeys. Microwires were chronically implanted in motor cortex to record neural activity and in cervical spinal cord to deliver electrical stimuli during voluntary wrist movements. Action potentials of 92 single cells were used to trigger stimuli at spinal sites, using either an autonomous electronic implant (the “Neurochip”) or laboratory instrumentation. The activity-dependent stimulation (10-400 A, 1-3 pulses/spike) produced responses in multiple finger and wrist muscles (both activation and suppression), and modulated hand movements. Monkeys performed a 2D center-out torque tracking task about the wrist, with and without the artificial CS connection. Many cells changed their tuning properties in the flexion-extension and radial-ulnar plane with the novel CS connection. Changes in tuning properties depended upon spinal output effects. The depth of tuning tended to decrease or increase when the preferred directions of cell and spinal output were matched or mismatched, respectively. One group of cells resumed their baseline tuning properties after the artificial connection was turned off. A second group maintained the pattern of activity acquired during the connection, even after it was turned off. These changes occurred when the connection was established for short periods in the lab, and were more pronounced after continuous operation of the Neurochip connection during free behavior in the home cage. Responses to spinal stimulation decreased after prolonged operation of the artificial CS connection. These results indicate that changes in CS control can be induced by artificial CS connections, and suggest a potential neuroprosthetic treatment for patients with damaged motor pathways. doi:10.1016/j.neures.2010.07.2234
e149
P1-h02 An alternative explanation of movement encoding in monkey’s primary motor cortex using joint angular velocity and joint torque during reaching tasks Hiroshi Ueda , Naoki Arai, Yuji Tamura, Eizo Miyashita Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan Studies on primate brains have been revealed that the primary motor cortex (M1) plays a significant role in the execution of voluntary movements such as reaching toward and grasping an object. Although a considerable number of hypotheses have been attempted to explain its mechanism of generating such movements, an explicit consensus is yet to be reached especially regarding what information is coded in the sequence of action potential. In the previous study, we have demonstrated that the neuronal firing rates of the arm region of monkey’s M1 during an ordinary center-out reaching task are well explained with a linear combination of shoulder-elbow joint angular velocity and its joint torque. Furthermore, the results are even better when considering the extension and flexion parts of the shoulder and elbow movements separately (i.e., we constructed 4 more sub-models based on the assumption that each neuron encodes only single direction of the movements, either extension or flexion, of the both shoulder and elbow joints). To ensure these results, in this experiment, we have developed a robot arm, which can exert a specified amount of force on the hand during reaching tasks, and tested our model under two additional experimental conditions: 1) application of a different amount of force (0, 1.75, 3.5N) on the hand, and 2) use of two workspaces (left and right). Twenty units has been recorded from the left hemisphere of a monkey so far, and the results were consistent with our previous experiment; the model with joint angular velocity and joint torque showed again convincingly good performance even under the additional experimental settings, and the majority (85%) of the neurons were even better explained with the direction selective (extension or flexion) models. These results suggest a reconsideration of the conventional viewpoints that M1 encodes kinematic variables in an isotonic task condition and static ones in an isometric task condition. doi:10.1016/j.neures.2010.07.2235
P1-h03 Feedback gains are time-scheduled in monkey reaching movements Yuki Ueyama , Eizo Miyashita Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan Control models of reaching arm movements are mainly categorized into two types. One is a trajectory-based control model (TBC) that requires a trajectory planning. The other is a non trajectory-based control model such as optimal feedback control (OFC). OFC schedules time-varying feedback gains minimizing a cost function in the motor planning and generates motor commands using estimated states as a state feedback. The purpose of this work is to obtain evidence demonstrating which control model is more plausible for the movement control. Although both models contain two types of controller (i.e., feedforward and sensory feedback controllers), features of the sensory feedback gains are different between the models. According to OFC, the sensory feedback gains are time-varying. On the other hand, TBC does not explicitly define the feedback gains. In this study, we estimated a Japanese monkey’s arm stiffness as positional sensory feedback gains during the reaching movement using a manipulandum that was able to cancel its dynamics and to apply perturbations to the monkey’s hand. The arm stiffness was estimated from hand trajectories and forces at 50–70 ms after perturbation because the somatosensory feedback was observed to follow the perturbation after a delay of about 20 ms. As a result, the values of stiffness of shoulder single-joint for forward reaching at the initiation, mid, and termination phases which were perturbed at 0, 100, and 250 ms after movement onset were 6.6 ± 2.0, 0.8 ± 0.9 and 5.4 ± 1.7 (mean ± SD) Nm/rad, respectively. In addition, the values of stiffness of elbow single-joint and each double-joint also showed similar trends. Thus, the arm stiffness as the positional sensory feedback gains was time-varying during the reaching movement. These results suggest that time-varying feedback gains are scheduled in the motor planning and OFC is a plausible model for the movement control. doi:10.1016/j.neures.2010.07.2236
P1-g18 Optogenetically induced suppression of neural activity in the macaque motor cortex Masaharu Kinoshita 1 , Katsuyuki Kaneda 1 , Hironori Kasahara 3 , Nobuhiko Hatanaka 2 , Ryosuke Matsui 3 , Satomi Chiken 2 , Kaoru Isa 1 , Hiroaki Mizukami 4 , Keiya Ozawa 4 , Dai Watanabe 3 , Atsushi Nambu 2 , Tadashi Isa 1 1
Dept. Dev. Physiol., NIPS, Okazaki, Japan 2 System Neurophysiol, NIPS, Okazaki, Japan 3 Lab Neurosci, Grad Sch Biostudies, Kyoto Univ, Kyoto, Japan 4 Div Genetic Therap, Ctr Molecular Medicine, Jichi Medical Univ., Tochigi, Japan The methods to selectively block spiking activities in the central nervous system are the powerful tools for investigating the functions of neural circuits in the brain. Recently, halorhodopsin (NpHR), a light-sensitive chloride pump of Natronomonas pharaonis, was found to be activated by yellow light (∼580nm) and activation of NpHR expressed in neurons led to hyperpolarization effective enough for suppression of the spiking activity. This optogenetic method allows us to recoverable and precise timing control of the selective blockade of spiking activity in the identified neurons. In this study, we tried to express eNpHR, a modified NpHR that contains membrane-trafficking signal sequences, in the hand-region of the primary motor cortex (M1) of macaque monkeys with viral vectors and tested the possibilities of photo-induced blockade of neural activities. In the monkey, neurons in the hand region of M1 send descending commands of finger movements to motor neurons innervating hand muscles. We have introduced eNpHR into the hand region of M1 of macaque monkeys with lentivirus vector with CaMKII␣ promoter to block the activity of cortical neurons involved in the control of hand movements. One month after the injection, we found that spike activity of the M1 neurons, induced by electrical stimulation of the premotor cortex, was successfully suppressed by applying the yellow laser with an optorode, a thin metal electrode combined with an optical fiber. This result will open up a new field of neuroscience research by enabling the neural pathway-specific blockade of signal transmission in macaque monkeys. doi:10.1016/j.neures.2010.07.2233
P1-h01 Changes in directional tuning of primate motor cortex cells driving an artificial corticospinal connection Yukio Nishimura 1,2 , Steve I. Perlmutter 1 , Eberhard E. Fetz 1 1
Department of Physiology & Biophysics and Washington National Primate Research Center, University of Washington, Seattle, Washington, USA 2 PRESTO, Japan Science and Technology Agency, Chiyoda, Tokyo, Japan In primates, corticospinal (CS) connections are essential to control forelimb movements. Patients with damaged CS pathways exhibit severe motor deficits, and might benefit from artificial connections. We investigated effects of introducing novel CS connections in 2 intact monkeys. Microwires were chronically implanted in motor cortex to record neural activity and in cervical spinal cord to deliver electrical stimuli during voluntary wrist movements. Action potentials of 92 single cells were used to trigger stimuli at spinal sites, using either an autonomous electronic implant (the “Neurochip”) or laboratory instrumentation. The activity-dependent stimulation (10-400 A, 1-3 pulses/spike) produced responses in multiple finger and wrist muscles (both activation and suppression), and modulated hand movements. Monkeys performed a 2D center-out torque tracking task about the wrist, with and without the artificial CS connection. Many cells changed their tuning properties in the flexion-extension and radial-ulnar plane with the novel CS connection. Changes in tuning properties depended upon spinal output effects. The depth of tuning tended to decrease or increase when the preferred directions of cell and spinal output were matched or mismatched, respectively. One group of cells resumed their baseline tuning properties after the artificial connection was turned off. A second group maintained the pattern of activity acquired during the connection, even after it was turned off. These changes occurred when the connection was established for short periods in the lab, and were more pronounced after continuous operation of the Neurochip connection during free behavior in the home cage. Responses to spinal stimulation decreased after prolonged operation of the artificial CS connection. These results indicate that changes in CS control can be induced by artificial CS connections, and suggest a potential neuroprosthetic treatment for patients with damaged motor pathways. doi:10.1016/j.neures.2010.07.2234
e149
P1-h02 An alternative explanation of movement encoding in monkey’s primary motor cortex using joint angular velocity and joint torque during reaching tasks Hiroshi Ueda , Naoki Arai, Yuji Tamura, Eizo Miyashita Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan Studies on primate brains have been revealed that the primary motor cortex (M1) plays a significant role in the execution of voluntary movements such as reaching toward and grasping an object. Although a considerable number of hypotheses have been attempted to explain its mechanism of generating such movements, an explicit consensus is yet to be reached especially regarding what information is coded in the sequence of action potential. In the previous study, we have demonstrated that the neuronal firing rates of the arm region of monkey’s M1 during an ordinary center-out reaching task are well explained with a linear combination of shoulder-elbow joint angular velocity and its joint torque. Furthermore, the results are even better when considering the extension and flexion parts of the shoulder and elbow movements separately (i.e., we constructed 4 more sub-models based on the assumption that each neuron encodes only single direction of the movements, either extension or flexion, of the both shoulder and elbow joints). To ensure these results, in this experiment, we have developed a robot arm, which can exert a specified amount of force on the hand during reaching tasks, and tested our model under two additional experimental conditions: 1) application of a different amount of force (0, 1.75, 3.5N) on the hand, and 2) use of two workspaces (left and right). Twenty units has been recorded from the left hemisphere of a monkey so far, and the results were consistent with our previous experiment; the model with joint angular velocity and joint torque showed again convincingly good performance even under the additional experimental settings, and the majority (85%) of the neurons were even better explained with the direction selective (extension or flexion) models. These results suggest a reconsideration of the conventional viewpoints that M1 encodes kinematic variables in an isotonic task condition and static ones in an isometric task condition. doi:10.1016/j.neures.2010.07.2235
P1-h03 Feedback gains are time-scheduled in monkey reaching movements Yuki Ueyama , Eizo Miyashita Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan Control models of reaching arm movements are mainly categorized into two types. One is a trajectory-based control model (TBC) that requires a trajectory planning. The other is a non trajectory-based control model such as optimal feedback control (OFC). OFC schedules time-varying feedback gains minimizing a cost function in the motor planning and generates motor commands using estimated states as a state feedback. The purpose of this work is to obtain evidence demonstrating which control model is more plausible for the movement control. Although both models contain two types of controller (i.e., feedforward and sensory feedback controllers), features of the sensory feedback gains are different between the models. According to OFC, the sensory feedback gains are time-varying. On the other hand, TBC does not explicitly define the feedback gains. In this study, we estimated a Japanese monkey’s arm stiffness as positional sensory feedback gains during the reaching movement using a manipulandum that was able to cancel its dynamics and to apply perturbations to the monkey’s hand. The arm stiffness was estimated from hand trajectories and forces at 50–70 ms after perturbation because the somatosensory feedback was observed to follow the perturbation after a delay of about 20 ms. As a result, the values of stiffness of shoulder single-joint for forward reaching at the initiation, mid, and termination phases which were perturbed at 0, 100, and 250 ms after movement onset were 6.6 ± 2.0, 0.8 ± 0.9 and 5.4 ± 1.7 (mean ± SD) Nm/rad, respectively. In addition, the values of stiffness of elbow single-joint and each double-joint also showed similar trends. Thus, the arm stiffness as the positional sensory feedback gains was time-varying during the reaching movement. These results suggest that time-varying feedback gains are scheduled in the motor planning and OFC is a plausible model for the movement control. doi:10.1016/j.neures.2010.07.2236