Publications by authors named "Tomoki W Suzuki"

8 Publications

  • Page 1 of 1

Effects of Optogenetic Suppression of Cortical Input on Primate Thalamic Neuronal Activity during Goal-Directed Behavior.

eNeuro 2021 Mar-Apr;8(2). Epub 2021 Mar 23.

Department of Physiology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.

The motor thalamus relays signals from subcortical structures to the motor cortical areas. Previous studies in songbirds and rodents suggest that cortical feedback inputs crucially contribute to the generation of movement-related activity in the motor thalamus. In primates, however, it remains uncertain whether the corticothalamic projections may play a role in shaping neuronal activity in the motor thalamus. Here, using an optogenetic inactivation technique with the viral vector system expressing halorhodopsin, we investigated the role of cortical input in modulating thalamic neuronal activity during goal-directed behavior. In particular, we assessed whether the suppression of signals originating from the supplementary eye field at the corticothalamic terminals could change the task-related neuronal modulation in the oculomotor thalamus in monkeys performing a self-initiated saccade task. We found that many thalamic neurons exhibited changes in their firing rates depending on saccade direction or task event, indicating that optical stimulation exerted task-specific effects on neuronal activity beyond the global changes in baseline activity. These results suggest that the corticothalamic projections might be actively involved in the signal processing necessary for goal-directed behavior. However, we also found that some thalamic neurons exhibited overall, non-task-specific changes in the firing rate during optical stimulation, even in control animals without vector injections. The stimulation effects in these animals started with longer latency, implying a possible thermal effect on neuronal activity. Thus, our results not only reveal the importance of direct cortical input in neuronal activity in the primate motor thalamus, but also provide useful information for future optogenetic studies.
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http://dx.doi.org/10.1523/ENEURO.0511-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009665PMC
March 2021

Roles of the Cerebellum in Motor Preparation and Prediction of Timing.

Neuroscience 2020 Apr 30. Epub 2020 Apr 30.

Department of Physiology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.

The cerebellum is thought to have a variety of functions because it developed with the evolution of the cerebrum and connects with different areas in the frontoparietal cortices. Like neurons in the cerebral cortex, those in the cerebellum also exhibit strong activity during planning in addition to the execution of movements. However, their specific roles remain elusive. In this article, we review recent findings focusing on preparatory activities found in the primate deep cerebellar nuclei during tasks requiring deliberate motor control and temporal prediction. Neurons in the cerebellum are active during anti-saccade preparation and their inactivation impairs proactive inhibitory control for saccades. Experiments using a self-timing task show that there are mechanisms for tracking elapsed time and regulating trial-by-trial variation in timing, and that the cerebellum is involved in the latter. When predicting the timing of periodic events, the cerebellum provides more accurate temporal information than the striatum. During a recently developed synchronized eye movement task, cerebellar nuclear neurons exhibited periodic preparatory activity for predictive synchronization. In all cases, the cerebellum generated preparatory activity lasting for several hundred milliseconds. These signals may regulate neuronal activity in the cerebral cortex that adjusts movement timing and predicts the timing of rhythmic events.
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http://dx.doi.org/10.1016/j.neuroscience.2020.04.039DOI Listing
April 2020

Neural oscillations in the primate caudate nucleus correlate with different preparatory states for temporal production.

Commun Biol 2019 14;2:102. Epub 2019 Mar 14.

Department of Physiology, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan.

When measuring time, neuronal activity in the cortico-basal ganglia pathways has been shown to be temporally scaled according to the interval, suggesting that signal transmission within the pathways is flexibly controlled. Here we show that, in the caudate nuclei of monkeys performing a time production task with three different intervals, the magnitude of visually-evoked potentials at the beginning of an interval differed depending on the conditions. Prior to this response, the power of low frequency components (6-20 Hz) significantly changed, showing inverse correlation with the visual response gain. Although these components later exhibited time-dependent modification during self-timed period, the changes in spectral power for interval conditions qualitatively and quantitatively differed from those associated with the reward amount. These results suggest that alteration of network state in the cortico-basal ganglia pathways indexed by the low frequency oscillations may be crucial for the regulation of signal transmission and subsequent timing behavior.
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http://dx.doi.org/10.1038/s42003-019-0345-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418172PMC
April 2020

Different contributions of preparatory activity in the basal ganglia and cerebellum for self-timing.

Elife 2018 07 2;7. Epub 2018 Jul 2.

Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan.

The ability to flexibly adjust movement timing is important for everyday life. Although the basal ganglia and cerebellum have been implicated in monitoring of supra- and sub-second intervals, respectively, the underlying neuronal mechanism remains unclear. Here, we show that in monkeys trained to generate a self-initiated saccade at instructed timing following a visual cue, neurons in the caudate nucleus kept track of passage of time throughout the delay period, while those in the cerebellar dentate nucleus were recruited only during the last part of the delay period. Conversely, neuronal correlates of trial-by-trial variation of self-timing emerged earlier in the cerebellum than the striatum. Local inactivation of respective recording sites confirmed the difference in their relative contributions to supra- and sub-second intervals. These results suggest that the basal ganglia may measure elapsed time relative to the intended interval, while the cerebellum might be responsible for the fine adjustment of self-timing.
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http://dx.doi.org/10.7554/eLife.35676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050043PMC
July 2018

[Neural Mechanisms of Temporal Monitoring and Prediction].

Brain Nerve 2017 Nov;69(11):1213-1222

Department of Physiology, Hokkaido University School of Medicine.

When waiting for a traffic light or dancing to a musical beat, we unconsciously keep track of elapsed time and precisely predict the timing of forthcoming sensory events. Temporal monitoring and prediction are integral to our daily life, and are regulated by neuronal processes through multiple global networks involving the frontoparietal cortices, the basal ganglia and the cerebellum. These processes are also known to be influenced by a variety of internal state and neuromodulators. Here, we review recent advance of research in the field.
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http://dx.doi.org/10.11477/mf.1416200898DOI Listing
November 2017

Causal Role of Noradrenaline in the Timing of Internally Generated Saccades in Monkeys.

Neuroscience 2017 Dec 9;366:15-22. Epub 2017 Oct 9.

Department of Physiology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. Electronic address:

We recently found that when monkeys performed an oculomotor version of the time production task, the trial-by-trial latency of self-timed saccades was negatively correlated with pupil diameter just before the delay period (Suzuki et al., 2016). Since pupil diameter has been shown to correlate with neuronal activity in the locus coeruleus, the level of noradrenaline (NA) in the brain might regulate the subjective passage of time. To examine this, we orally administered a selective noradrenaline reuptake inhibitor (reboxetine, 0.4-0.8 mg) when animals made a self-initiated memory-guided saccade >1 s following the appearance of a brief visual cue. We found that reboxetine delayed self-timed saccades, while the latency of visually triggered saccades remained unchanged. Because the changes in proportions and latencies of early impulsive saccades were comparable between conditions with and without drug administration, alteration of self-timing might not result from reduced impulsivity. We also assessed other behavioral parameters (saccade accuracy, velocity, and latency variance), but failed to find any drug effect except for the accuracy of visually triggered saccades in the high-dose condition, indicating that reboxetine specifically altered self-timing under our experimental conditions. Our results suggest that NA-related internal states may causally regulate temporal information processing in the brain.
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http://dx.doi.org/10.1016/j.neuroscience.2017.10.003DOI Listing
December 2017

Correlation between Pupil Size and Subjective Passage of Time in Non-Human Primates.

J Neurosci 2016 11;36(44):11331-11337

Department of Physiology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, and

Our daily experience of time is strongly influenced by internal states, such as arousal, attention, and mood. However, the underlying neuronal mechanism remains largely unknown. To investigate this, we recorded pupil diameter, which is closely linked to internal factors and neuromodulatory signaling, in monkeys performing the oculomotor version of the time production paradigm. In the self-timed saccade task, animals were required to make a memory-guided saccade during a predetermined time interval following a visual cue. We found that pupil diameter was negatively correlated with trial-by-trial latency of self-timed saccades. Because no significant correlation was found for visually guided saccades, correlation of self-timed saccades could not be explained solely by the facilitation of saccade execution. As the reward amount was manipulated, pupil diameter and saccade latency altered in opposite directions and the magnitudes of modulation correlated strongly across sessions, further supporting the close link between pupil diameter and the subjective passage of time. When the animals were trained to produce two different intervals depending on the instruction, the pupil size again correlated with the trial-by-trial variation of saccade latency in each condition; however, pupil diameter differed significantly for saccades with similar latencies generated under different conditions. Our results indicate that internal brain states indexed by pupil diameter, which parallel noradrenergic neuronal activity (Aston-Jones and Cohen, 2005), may bias trial-by-trial variation in the subjective passage of time.

Significance Statement: Daily experience of time is strongly influenced by our internal state, but the underlying neuronal mechanism remains elusive. Here we demonstrate that pupil diameter is negatively correlated with subjective elapsed time in monkeys performing an oculomotor version of the time production task. When the animals reported two different intervals depending on the instruction, pupil size was correlated with reported timing in each condition but differed for similar timing under different conditions. Given the close correlation between pupil diameter and noradrenergic signaling reported previously, our data indicate that brain states probed by pupil diameter and noradrenergic neuronal activity might modulate subjective passage of time.
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http://dx.doi.org/10.1523/JNEUROSCI.2533-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601963PMC
November 2016

Implications of Lateral Cerebellum in Proactive Control of Saccades.

J Neurosci 2016 06;36(26):7066-74

Department of Physiology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, and

Unlabelled: Although several lines of evidence establish the involvement of the medial and vestibular parts of the cerebellum in the adaptive control of eye movements, the role of the lateral hemisphere of the cerebellum in eye movements remains unclear. Ascending projections from the lateral cerebellum to the frontal and parietal association cortices via the thalamus are consistent with a role of these pathways in higher-order oculomotor control. In support of this, previous functional imaging studies and recent analyses in subjects with cerebellar lesions have indicated a role for the lateral cerebellum in volitional eye movements such as anti-saccades. To elucidate the underlying mechanisms, we recorded from single neurons in the dentate nucleus of the cerebellum in monkeys performing anti-saccade/pro-saccade tasks. We found that neurons in the posterior part of the dentate nucleus showed higher firing rates during the preparation of anti-saccades compared with pro-saccades. When the animals made erroneous saccades to the visual stimuli in the anti-saccade trials, the firing rate during the preparatory period decreased. Furthermore, local inactivation of the recording sites with muscimol moderately increased the proportion of error trials, while successful anti-saccades were more variable and often had shorter latency during inactivation. Thus, our results show that neuronal activity in the cerebellar dentate nucleus causally regulates anti-saccade performance. Neuronal signals from the lateral cerebellum to the frontal cortex might modulate the proactive control signals in the corticobasal ganglia circuitry that inhibit early reactive responses and possibly optimize the speed and accuracy of anti-saccades.

Significance Statement: Although the lateral cerebellum is interconnected with the cortical eye fields via the thalamus and the pons, its role in eye movements remains unclear. We found that neurons in the caudal part of the lateral (dentate) nucleus of the cerebellum showed the increased firing rate during the preparation of anti-saccades. Inactivation of the recording sites modestly elevated the rate of erroneous saccades to the visual stimuli in the anti-saccade trials, while successful anti-saccades during inactivation tended to have a shorter latency. Our data indicate that neuronal signals in the lateral cerebellum may proactively regulate anti-saccade generation through the pathways to the frontal cortex, and may inhibit early reactive responses and regulate the accuracy of anti-saccades.
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http://dx.doi.org/10.1523/JNEUROSCI.0733-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604892PMC
June 2016