Marc Deffains

Hebrew University of Jerusalem, Yerushalayim, Jerusalem, Israel

Are you Marc Deffains?

Claim your profile

Publications (8)31.05 Total impact

  • Marc Deffains · Hagai Bergman
    [Show abstract] [Hide abstract]
    ABSTRACT: Basal ganglia disorders such as Parkinson's disease, dystonia, and Huntington's disease are characterized by a dysregulation of the basal ganglia neuromodulators (dopamine, acetylcholine, and others), which impacts cortico-striatal transmission. Basal ganglia disorders are often associated with an imbalance between the midbrain dopaminergic and striatal cholinergic systems. In contrast to the extensive research and literature on the consequences of a malfunction of midbrain dopaminergic signaling on the plasticity of the cortico-striatal synapse, very little is known about the role of striatal cholinergic interneurons in normal and pathological control of cortico-striatal transmission. In this review, we address the functional role of striatal cholinergic interneurons, also known as tonically active neurons and attempt to understand how the alteration of their functional properties in basal ganglia disorders leads to abnormal cortico-striatal synaptic plasticity. Specifically, we suggest that striatal cholinergic interneurons provide a permissive signal, which enables long-term changes in the efficacy of the cortico-striatal synapse. We further discuss how modifications in the striatal cholinergic activity pattern alter or prohibit plastic changes of the cortico-striatal synapse. Long-term cortico-striatal synaptic plasticity is the cellular substrate of procedural learning and adaptive control behavior. Hence, abnormal changes in this plasticity may underlie the inability of patients with basal ganglia disorders to adjust their behavior to situational demands. Normalization of the cholinergic modulation of cortico-striatal synaptic plasticity may be considered as a critical feature in future treatments of basal ganglia disorders. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 06/2015; DOI:10.1002/mds.26300 · 5.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The external segment of the globus pallidus (GPe) is one of the core nuclei of the basal ganglia, playing a major role in normal control of behavior and in the pathophysiology of basal ganglia-related disorders such as Parkinson's disease. In vivo, most neurons in the GPe are characterized by high firing rates (50-100 spikes/s), interspersed with long periods (∼0.6 s) of complete silence, which are termed GPe pauses. Previous physiological studies of single and pairs of GPe neurons have failed to fully disclose the physiological process by which these pauses originate. We examined 1001 simultaneously recorded pairs of high-frequency discharge GPe cells recorded from four monkeys during task-irrelevant periods, considering the activity in one cell while the other is pausing. We found that pauses (n = 137,278 pauses) coincide with a small yet significant reduction in firing rate (0.78 ± 0.136 spikes/s) in other GPe cells. Additionally, we found an increase in the probability of the simultaneously recorded cell to pause during the pause period of the "trigger" cell. Importantly, this increase in the probability to pause at the same time does not account for the reduction in firing rate by itself. Modeling of GPe cells as class 2 excitability neurons (Hodgkin, 1948) with common external inputs can explain our results. We suggest that common inputs decrease the GPe discharge rate and lead to a bifurcation phenomenon (pause) in some of the GPe neurons. Copyright © 2015 Schechtman et al.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2015; 35(17):6744-51. DOI:10.1523/JNEUROSCI.5232-14.2015 · 6.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In Parkinson's disease, pathological synchronous oscillations divide the subthalamic nucleus (STN) of patients into a dorsolateral oscillatory region and ventromedial non-oscillatory region. This bipartite division reflects the motor vs. the non-motor (associative/limbic) subthalamic areas, respectively. However, significant topographic differences in the neuronal discharge rate between these two STN sub-regions in Parkinsonian patients is still controversial. In this study, 119 STN microelectrode trajectories (STN length > 2mm, mean = 5.32mm) with discernible oscillatory and non-oscillatory regions were carried on 60 patients undergoing deep brain stimulation surgery for Parkinson's disease. 2137 and 2152 multi-unit stable signals were recorded (recording duration > 10s, mean = 21.25s) within the oscillatory and non-oscillatory STN regions, respectively. Spike detection and sorting was applied offline on every multi-unit stable signal using an automatic method with systematic quantification of the isolation quality (range = 0 to 1) of the identified units. In all, 3094 and 3130 units were identified in the oscillatory and non-oscillatory regions, respectively. On average, the discharge rate of better-isolated neurons (isolation score > 0.70) was higher in the oscillatory region than the non-oscillatory region (44.55 ± 0.87 versus 39.97 ± 0.77 spikes/s, N = 665 and 761, respectively). The discharge rate of the STN neurons was positively correlated to the strength of their own and their surrounding 13-30Hz beta oscillatory activity. Therefore, in the Parkinsonian STN, beta oscillations and higher neuronal discharge rate are correlated and coexist in the motor area of the STN compared to its associative/limbic area.
    Journal of Neurophysiology 06/2014; 112(6). DOI:10.1152/jn.00170.2014 · 3.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: You might find this additional info useful... This article cites 48 articles, 17 of which can be accessed free at:
  • Marc Deffains · Eric Legallet · Paul Apicella
    [Show abstract] [Hide abstract]
    ABSTRACT: The capacity to acquire motor skills through repeated practice of a sequence of movements underlies many everyday activities. Extensive research in humans has dealt with the importance of spatial and temporal factors on motor sequence learning, standing in contrast to the few studies available in animals, particularly in nonhuman primates. In the present experiments, we studied the effect of the serial order of stimuli and associated movements in macaque monkeys overtrained to make arm-reaching movements in response to spatially distinct visual targets. Under different conditions, the temporal structure of the motor sequence was varied by changing the duration of the interval between successive target stimuli or by adding a cue that reliably signaled the onset time of the forthcoming target stimulus. In each condition, the extent to which the monkeys are sensitive to the spatial regularities was assessed by comparing performance when stimulus locations follow a repeating sequence, as opposed to a random sequence. We observed no improvement in task performance on repeated sequence blocks, compared to random sequence blocks, when target stimuli are relatively distant from each other in time. On the other hand, the shortening of the time interval between successive target stimuli or, more efficiently, the addition of a temporal cue before the target stimulus yielded a performance advantage under repeated sequence, reflected in a decrease in the latency of arm and saccadic eye movements accompanied by an increased tendency for eye movements to occur in an anticipatory manner. Contrary to the effects on movement initiation, the serial order of stimuli and movements did not markedly affect the execution of movement. Moreover, the location of a given target in the random sequence influenced task performance based on the location of the preceding target, monkeys being faster in responding as a result of familiarity caused by extensive practice with some target transitions also used in the repeated sequence. This performance advantage was most prominently detectable when temporal prediction of forthcoming target stimuli was optimized. Taken together, the present findings demonstrate that the monkey's capacity to make use of serial order information to speed task performance was dependent on the temporal structure of the motor sequence.
    Experimental Brain Research 08/2011; 214(3):415-25. DOI:10.1007/s00221-011-2839-0 · 2.17 Impact Factor
  • Paul Apicella · Sabrina Ravel · Marc Deffains · Eric Legallet
    [Show abstract] [Hide abstract]
    ABSTRACT: The detection of differences between predictions and actual outcomes is important for associative learning and for selecting actions according to their potential future reward. There are reports that tonically active neurons (TANs) in the primate striatum may carry information about errors in the prediction of rewards. However, this property seems to be expressed in classical conditioning tasks but not during performance of an instrumental task. To address this issue, we recorded the activity of TANs in the putamen of two monkeys performing an instrumental task in which probabilistic rewarding outcomes were contingent on an action in block-design experiments. Behavioral evidence suggests that animals adjusted their performance according to the level of probability for reward on each trial block. We found that the TAN response to reward was stronger as the reward probability decreased; this effect was especially prominent on the late component of the pause-rebound pattern of typical response seen in these neurons. The responsiveness to reward omission was also increased with increasing reward probability, whereas there were no detectable effects on responses to the stimulus that triggered the movement. Overall, the modulation of TAN responses by reward probability appeared relatively weak compared with that observed previously in a probabilistic classical conditioning task using the same block design. These data indicate that instrumental conditioning was less effective at demonstrating prediction error signaling in TANs. We conclude that the sensitivity of the TAN system to reward probability depends on the specific learning situation in which animals experienced the stimulus-reward associations.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2011; 31(4):1507-15. DOI:10.1523/JNEUROSCI.4880-10.2011 · 6.75 Impact Factor
  • Marc Deffains · Eric Legallet · Paul Apicella
    [Show abstract] [Hide abstract]
    ABSTRACT: The striatum, especially its dorsolateral part, plays a major role in motor skill learning and habit formation, but it is still unclear how this contribution might be mediated at the neuronal level. We recorded single neurons in the posterior putamen of two monkeys performing an overlearned sequence of arm reaching movements to examine whether task-related activities are sensitive to manipulations of the serial order of stimulus-target locations. The monkeys' capacity to learn sequential regularities was assessed by comparing arm movement latencies and saccadic ocular reactions when a fixed repeating sequence was replaced with a random sequence. We examined neurons classified as phasically active projection neurons (PANs) and tonically active presumed cholinergic interneurons (TANs). About one-third of the PANs (35/106, 33%) activated during specific parts of a trial displayed modulations of their level of activation when the sequential structure was changed. This differential activity consisted of either decreases or increases in activity without altering the time period during which task-related activations occurred. In addition, half of the TANs (41/80, 51%) changed their responses to task stimuli with the sequence switch, indicating that the response selectivity of TANs reflects the detection of the context that requires adaptation to changes in the serial order of stimulus presentations. Our findings suggest that task-related changes in activity of projection neurons may be an important factor contributing to the production and adjustment of sequential behavior executed in an automatic fashion, whereas putative interneurons may provide a signal for performance monitoring in specific contexts.
    Journal of Neurophysiology 09/2010; 104(3):1355-69. DOI:10.1152/jn.00355.2010 · 3.04 Impact Factor
  • Source
    Paul Apicella · Marc Deffains · Sabrina Ravel · Eric Legallet
    [Show abstract] [Hide abstract]
    ABSTRACT: Tonically active neurons (TANs) in the primate striatum are responsive to rewarding stimuli and they are thought to be involved in the storage of stimulus-reward associations or habits. However, it is unclear whether these neurons may signal the difference between the prediction of reward and its actual outcome as a possible neuronal correlate of reward prediction errors at the striatal level. To address this question, we studied the activity of TANs from three monkeys trained in a classical conditioning task in which a liquid reward was preceded by a visual stimulus and reward probability was systematically varied between blocks of trials. The monkeys' ability to discriminate the conditions according to probability was assessed by monitoring their mouth movements during the stimulus-reward interval. We found that the typical TAN pause responses to the delivery of reward were markedly enhanced as the probability of reward decreased, whereas responses to the predictive stimulus were somewhat stronger for high reward probability. In addition, TAN responses to the omission of reward consisted of either decreases or increases in activity that became stronger with increasing reward probability. It therefore appears that one group of neurons differentially responded to reward delivery and reward omission with changes in activity into opposite directions, while another group responded in the same direction. These data indicate that only a subset of TANs could detect the extent to which reward occurs differently than predicted, thus contributing to the encoding of positive and negative reward prediction errors that is relevant to reinforcement learning.
    European Journal of Neuroscience 08/2009; 30(3):515-26. DOI:10.1111/j.1460-9568.2009.06872.x · 3.67 Impact Factor