scholarly journals Cerebellar climbing fibers encode expected reward size

2019 ◽  
Author(s):  
Noga Larry ◽  
Merav Yarkoni ◽  
Adi Lixenberg ◽  
Mati Joshua
Keyword(s):  
Associative Learning ◽  
Error Correction ◽  
Eye Movement ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
Successful Completion ◽  
General Role ◽  
Reward Delivery

Climbing fiber inputs to the cerebellum encode error signals that instruct learning. Recently, evidence has accumulated to suggest that the cerebellum is also involved in the processing of reward. To study how rewarding events are encoded, we recorded the activity of climbing fibers when monkeys were engaged in an eye movement task. At the beginning of each trial, the monkeys were cued the size of the reward that would be delivered upon successful completion of the trial. We found increased climbing fiber activity during cue presentation when information about reward size was first made available. Reward size did not modulate activity at reward delivery. These results indicate that climbing fibers encode the expected reward size and suggest a general role of the cerebellum in associative learning beyond error correction.

scholarly journals Cerebellar climbing fibers encode expected reward size

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Noga Larry ◽  
Merav Yarkoni ◽  
Adi Lixenberg ◽  
Mati Joshua
Keyword(s):  
Eye Movements ◽  
Error Correction ◽  
Large Reward ◽  
Small Reward ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
Successful Completion ◽  
General Role ◽  
Reward Delivery

Climbing fiber inputs to the cerebellum encode error signals that instruct learning. Recently, evidence has accumulated to suggest that the cerebellum is also involved in the processing of reward. To study how rewarding events are encoded, we recorded the activity of climbing fibers when monkeys were engaged in an eye movement task. At the beginning of each trial, the monkeys were cued to the size of the reward that would be delivered upon successful completion of the trial. Climbing fiber activity increased when the monkeys were presented with a cue indicating a large reward, but not a small reward. Reward size did not modulate activity at reward delivery or during eye movements. Comparison between climbing fiber and simple spike activity indicated different interactions for coding of movement and reward. These results indicate that climbing fibers encode the expected reward size and suggest a general role of the cerebellum in associative learning beyond error correction.

scholarly journals Gating of neural error signals during motor learning

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Rhea R Kimpo ◽  
Jacob M Rinaldi ◽  
Christina K Kim ◽  
Hannah L Payne ◽  
Jennifer L Raymond
Keyword(s):  
Motor Learning ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
Motor Memory ◽  
Ocular Reflex ◽  
Learning Tasks ◽  
Performance Errors ◽  
Vestibulo Ocular Reflex

Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors.

scholarly journals Complex spikes encode reward expectation signals during visuomotor association learning

2019 ◽  
Author(s):  
Naveen Sendhilnathan ◽  
Anna Ipata ◽  
Michael E. Goldberg
Keyword(s):  
Stimulus Onset ◽  
Higher Order ◽  
Independent Manner ◽  
General Role ◽  
Order Processing ◽  
Association Learning ◽  
Reward Delivery ◽  
Spike Signals ◽  
Complex Spikes

AbstractClimbing fiber input to Purkinje cells has been thought to instruct learning related changes in simple spikes and cause behavioral changes through an error-based learning mechanism. Although, this framework explains simple motor learning, it cannot be extended to learning higher-order skills. Recently the cerebellum has been implicated in a variety of cognitive tasks and reward-based learning. Here we show that when a monkey learns a new visuomotor association, complex spikes predict the time of the beginning of the trial in a learning independent manner as well as encode a learning contingent reward expectation signal after the stimulus onset and reward delivery. These complex spike signals are unrelated to and were unlikely to instruct the reward based signal found in the simple spikes. Our results provide a more general role of complex spikes in learning and higher-order processing while gathering evidence for their participation in reward based learning.

Dissent in the Atlantic World, 1787–1830

2018 ◽  
Author(s):  
Katherine Carté Engel
Keyword(s):  
United States ◽  
African Americans ◽  
First Amendment ◽  
Church And State ◽  
State Level ◽  
The United States ◽  
American Population ◽  
Simple Fact ◽  
General Role

The very term ‘Dissenter’ became problematic in the United States, following the passing of the First Amendment. The formal separation of Church and state embodied in the First Amendment was followed by the ending of state-level tax support for churches. None of the states established after 1792 had formal religious establishments. Baptists, Congregationalists, Presbyterians, and Methodists accounted for the majority of the American population both at the beginning and end of this period, but this simple fact masks an important compositional shift. While the denominations of Old Dissent declined relatively, Methodism grew quickly, representing a third of the population by 1850. Dissenters thus faced several different challenges. Primary among these were how to understand the idea of ‘denomination’ and also the more general role of institutional religion in a post-establishment society. Concerns about missions, and the positions of women and African Americans are best understood within this context.

scholarly journals Role of Primate Cerebellar Hemisphere in Voluntary Eye Movement Control Revealed by Lesion Effects

2009 ◽  
Vol 101 (2) ◽  
pp. 934-947 ◽  
Author(s):  
Masafumi Ohki ◽  
Hiromasa Kitazawa ◽  
Takahito Hiramatsu ◽  
Kimitake Kaga ◽  
Taiko Kitamura ◽  
...  
Keyword(s):  
Eye Movements ◽  
Eye Movement ◽  
Smooth Pursuit ◽  
Movement Control ◽  
Cerebellar Hemisphere ◽  
Target Velocity ◽  
Eye Movement Control ◽  
Pursuit Eye Movements ◽  
Catch Up

The anatomical connection between the frontal eye field and the cerebellar hemispheric lobule VII (H-VII) suggests a potential role of the hemisphere in voluntary eye movement control. To reveal the involvement of the hemisphere in smooth pursuit and saccade control, we made a unilateral lesion around H-VII and examined its effects in three Macaca fuscata that were trained to pursue visually a small target. To the step (3°)-ramp (5–20°/s) target motion, the monkeys usually showed an initial pursuit eye movement at a latency of 80–140 ms and a small catch-up saccade at 140–220 ms that was followed by a postsaccadic pursuit eye movement that roughly matched the ramp target velocity. After unilateral cerebellar hemispheric lesioning, the initial pursuit eye movements were impaired, and the velocities of the postsaccadic pursuit eye movements decreased. The onsets of 5° visually guided saccades to the stationary target were delayed, and their amplitudes showed a tendency of increased trial-to-trial variability but never became hypo- or hypermetric. Similar tendencies were observed in the onsets and amplitudes of catch-up saccades. The adaptation of open-loop smooth pursuit velocity, tested by a step increase in target velocity for a brief period, was impaired. These lesion effects were recognized in all directions, particularly in the ipsiversive direction. A recovery was observed at 4 wk postlesion for some of these lesion effects. These results suggest that the cerebellar hemispheric region around lobule VII is involved in the control of smooth pursuit and saccadic eye movements.

scholarly journals Tethering-induced destabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Atp Binding ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization ◽  
Lateral Sclerosis

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RNA-recognition-motif (RRM) domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), alzheimer's disease (AD) and Multisystem proteinopathy (MSP). Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: (1) upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. (2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity slightly higher to the tethered than isolated forms. (3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1–RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

Réponses évoquées par les mouvements oculaires d'exploration (réponse lambda): Rôle des afférences intervenant à divers moments du processus oculo-moteur

Perception ◽  
1972 ◽  
Vol 1 (2) ◽  
pp. 167-175 ◽  
Author(s):  
Nicole Lesèvre ◽  
A Rémond
Keyword(s):  
Eye Movements ◽  
Eye Movement ◽  
Visual Effects ◽  
Experimental Conditions ◽  
Initial Portion ◽  
Vertical Movements ◽  
Black Field ◽  
Fixation Points ◽  
Lambda Response

Experiments are reported the aim of which was to elucidate the cause of each of the components of the lambda response, and particularly to evaluate the role of ‘on’ and ‘off’ visual effects which appear at various times during the oculomotor process and also the possible influence of non-visual mechanisms. Eight subjects with normal sight were studied under the following conditions: (i) horizontal eye movements of 12° were guided by fixation points placed on a dimly-lit uniform black field of 20°; a checkerboard of 6° aperture was placed in this field so as to be integrated into the oculomotor process at different times—at the beginning, during and at the end of the eye movement; (ii) successive horizontal eye movements of 3°, 7° and 11° scanned a checkerboard of 20°, each square of which had a 40′ aperture; (iii) the checkerboard was moved with an amplitude and period similar to those of the eye movements in (ii), but this time with gaze fixed. Horizontal and vertical movements of both eyes were recorded with an EOG. An EEG of the parieto-occipital regions was obtained using eight linked bipolar derivations in line on two montages, median longitudinal and right-left transverse. The EEG and EOG data were digitalized and a numerical programme of waveform recognition was used to identify the beginning of the saccade which triggers the averaging out of the EEG before (100 ms) and after (500 ms) the eye movement. A discussion of the results, taking into account the latency of the different components and their reinforcements or inhibition depending on experimental conditions, suggests that the two initial components of lambda response (including the initial portion of the classical lambda wave) might be due to visual effects (‘off effect’) that arise at the start of the movement or slightly before it at the time that the saccadic suppression begins. The later components could be attributed to visual effects brought into play towards the end of the movement (‘on effect’), when perception becomes normal again. It is, however, difficult to explain some of the results related to the amplitude of lambda components without bringing in a mechanism of non-visual origin (corollary discharge).

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