Influence of Predictive Information on Responses of Tonically Active Neurons in the Monkey Striatum

Paul Apicella1, Sabrina Ravel1, Pierangelo Sardo2, and Eric Legallet1

1 Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, Centre National de la Recherche Scientifique, 13402 Marseille Cedex 20, France; and 2 Istituto di Fisiologia Umana, Università di Palermo, 90134 Palermo, Italy

    ABSTRACT
Abstract
Introduction
Methods
Results
Discussion
References

Apicella, Paul, Sabrina Ravel, Pierangelo Sardo, and Eric Legallet. Influence of predictive information on responses of tonically active neurons in the monkey striatum. J. Neurophysiol. 80: 3341-3344, 1998. We investigated how the expectation of a signal of behavioral significance influences the activity of tonically active neurons in the striatum of two monkeys performing a simple reaction time task under two conditions, an uncued condition in which the trigger stimulus occurred randomly in time and a cued condition in which the same trigger was preceded by an instruction stimulus serving as a predictive signal for the forthcoming signal eliciting an immediate behavioral reaction. Both monkeys benefited from the presence of the instruction stimulus to reduce their reaction time, suggesting an increased ability to predict the trigger onset during cued trials compared with uncued trials. A majority of neurons (199/272, 73%) showed a phasic reduction in activity after the onset of the trigger stimulus in the uncued condition, whereas only 38% responded to the same stimulus when it was preceded by the instruction. Furthermore, magnitudes of trigger responses in the uncued condition were significantly higher than in the cued condition. Fifty-seven percent of the neurons responded to the instruction stimulus, and one-half of the neurons losing their response to the trigger in the cued condition responded to the instruction stimulus. These findings suggest that responses of tonic striatal neurons to a trigger stimulus for movement were influenced by predictive information.

    INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References

Previous single neuron recording studies in behaving monkeys have shown that a particular class of striatal neurons, called tonically active neurons, respond to stimuli associated with reward (Aosaki et al. 1994; Apicella et al. 1996; Kimura et al. 1984) and to the reward itself (Apicella et al. 1997). There is evidence that responses of these neurons to rewarding stimuli show specificities depending on the instruction context in which they occur (Apicella et al. 1991). Furthermore, most of these neurons did not respond unconditionally to the delivery of a liquid reward because responses predominantly occurred if the liquid was delivered outside of any behavioral task (Apicella et al. 1997). It therefore appeared that the neuronal responses were influenced by the context in which relevant stimuli were presented. The purpose of this study was to investigate how the expectation of a predictable conditioned stimulus may influence neuronal responsiveness to this stimulus. To this end, we compared the activity of tonic striatal neurons during performance of a simple reaction time task in the presence and absence of an instruction cue presented at a fixed interval before a trigger stimulus for movement. The results showed that the trigger stimulus modulated many neurons when its onset remained unpredictable, whereas the same stimulus modulated fewer neurons and at lower magnitudes when it was preceded by an instruction cue.


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FIG. 1. A: histological reconstruction of recording positions of tonic striatal neurons. Four representative coronal sections are shown from one monkey. Dots: neurons responding to the trigger stimulus; lines: unresponsive neurons. B: influence of task condition on the responses of two tonic striatal neurons to the trigger stimulus. Both neurons showed a strong response to the trigger stimulus in the uncued condition. This response disappeared completely (top) or decreased (bottom) while testing the same neurons in the cued condition. In this and the following figure, dot displays are shown below perievents time histograms. Each dot represents a neuronal impulse, and each line of dots represents one trial. Rasters and histograms are aligned on the presentation of the trigger stimulus, and the original sequence of trials is shown from top to bottom in rasters. Vertical calibration is 10 impulses/bin for all histograms. Binwidth of histograms is 10 ms.


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FIG. 2. Activity of 2 tonic striatal neurons after the instruction and trigger stimuli during performance of the reaction time task in the cued condition. Top: response to the instruction stimulus, but no response to the subsequent trigger stimulus. Bottom: responses both to the instruction and to the trigger stimuli.

    METHODS
Abstract
Introduction
Methods
Results
Discussion
References

Two male monkeys (Macaca fascicularis, 5-6 kg) were trained to make an arm reaching movement in response to a visual stimulus to obtain a liquid reward. This study was performed in accordance with the NIH guide for the care and use of laboratory animals and the French laws on animal experimentations. The monkey was seated in a restraining box facing a vertical panel. For initiation of a trial, the animal had to keep its hand on a key located on the lower part of the panel. This was followed by illumination of a red light-emitting diode (LED) serving as a signal for the monkey to trigger an arm movement toward a target positioned just below the illuminated LED. Fruit juice was given as reinforcement when the monkey's hand contacted the target. Each monkey was subjected to two task conditions, with visual stimuli always presented at the same spatial location across trials; 1) in the uncued condition, the interval between the onset of the trigger stimulus and the start of the trial varied randomly from trial to trial (0.5-2.0 s), and no external cue predicting the trigger onset was available, and, 2) in the cued condition, the onset of a green light, at the start of each trial, was followed after a fixed interval of 1.5 s by the presentation of the trigger stimulus. In this case, the first stimulus in each trial became an instruction cue signaling that the trigger stimulus was about to be presented. The cued condition alternated with the uncued condition in blocks of 30-40 trials. Task performance was assessed in terms of reaction time (from trigger onset to key release). Median (50th percentile) reaction times were calculated for each block of trials and each task condition, and 45-47 blocks, distributed throughout the data collection period, were selected for behavioral analysis.

At the completion of training in the two task conditions, a stainless steel chamber was implanted under sodium pentobarbital anesthesia (35 mg/kg iv). Glass-coated tungsten microelectrodes were inserted through the dura mater into the striatum with a hydraulic microdrive to record neuronal activity with conventional single neuron recording techniques. The entire experiment was controlled on-line by a minicomputer, which triggered the visual stimuli, delivered the liquid reward, and collected the signals from neuronal activity.

Neuronal responsiveness was assessed both in terms of percentages of responding neurons and magnitudes of changes for every responding neuron. Baseline activity was determined in the 0.5-s interval that immediately preceded the first stimulus in each task condition. A test window with a duration of 100 ms was moved in 10-ms steps starting at the presentation of each visual stimulus. The onset of a response was taken to be the beginning of the first of five consecutive steps showing a significant difference against the baseline activity (P < 0.05, Wilcoxon signed-rank test). Response offset was determined in the same way by searching for any loss of statistically significant differences during five steps. Magnitude of response was assessed by counting spikes between onset and offset of responses and expressed as percentage below baseline activity.

After completion of neuronal recording, monkeys were deeply anesthetized with sodium pentobarbital and transcardially perfused with saline followed by 4% paraformaldehyde. Coronal sections of the brain (50 µm thick) were made with a freezing microtome and stained with cresyl violet.

    RESULTS
Abstract
Introduction
Methods
Results
Discussion
References

During task performance, reaction times were significantly shorter in the cued condition than in the uncued condition (P < 0.01, Wilcoxon test). In the first monkey, mean reaction time in the uncued condition was 280 ± 15 ms compared with 245 ± 21 ms in the cued condition. In the second monkey, the respective values were 322 ± 25 and 308 ± 25 ms. These differences in the latency to react to the trigger stimulus suggest that the presence of the instruction cue allows the monkeys to predict the trigger onset, such a predictive ability leading to a shortening of reaction time.

A total of 272 tonically active neurons (putamen, n = 193; caudate nucleus, n = 79) were tested in both the cued and uncued conditions. In agreement with previous descriptions (Alexander and DeLong 1985; Hikosaka et al. 1989; Kimura et al. 1984), these neurons displayed specific electrophysiological characteristics, discharging impulses with low frequencies (7.6 ± 2.3 impulses/s) and relatively long duration (initial negative phase: 655 ± 89 µs, 200- to 1,500-Hz filtering). They contrasted with slowly discharging striatal neurons, which discharged shorter impulses at rates below 1/s. Figure 1A illustrates the recording sites of a sample of tonic striatal neurons. It can be seen that most of the neurons recorded in this monkey were located in dorsal and medial putamen.

Responses to the trigger stimulus

During task performance 199 of the 272 neurons (73%) showed a phasic reduction in activity after onset of the trigger stimulus in the uncued condition. By contrast, only 103 neurons (38%) responded to the trigger stimulus when it was preceded by the instruction stimulus in the cued condition. In detail, 102 neurons displayed responses exclusively in the uncued condition, and 97 neurons remained responsive in both task conditions. Magnitudes of trigger responses amounted to a decrease of -61 ± 16% (mean ± SD) and -53 ± 20% in the uncued and cued conditions respectively, this difference being statistically significant (P < 0.01, one-way analysis of variance followed by Fisher test). Figure 1B illustrates the influence of testing condition for two neurons that responded to the trigger in the uncued condition. The first neuron (Fig. 1B, top) completely lost its response in the cued condition, whereas the second neuron (bottom) responded rather weakly when the trigger was presented in the cued condition, in comparison with its response in the uncued condition.

Responses to the instruction stimulus

In the cued condition, 154 neurons (57%) responded to the instruction stimulus presented at a fixed interval before the trigger stimulus. Among them, 84 were modulated exclusively after onset of the instruction stimulus, and 70 displayed separate responses to the instruction and the trigger stimuli. Examples of each category are illustrated in Fig. 2. One-half of the neurons (51/102, 50%) losing their responses to the trigger in the cued condition responded to the instruction stimulus. Magnitudes of instruction responses amounted to a decrease of -59 ± 19%. There were no significant differences in magnitudes of changes between instruction responses in the cued condition and trigger responses in the uncued condition (P > 0.05), and such a difference was significant between instruction and trigger responses in the cued condition (P < 0.01).

    DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References

Our objective was to examine the influence of predictive information on responses of tonically active neurons in the primate striatum to a stimulus eliciting a movement. That the monkey used the predictive information was confirmed by measuring the reaction times of movement. The instruction presented before the trigger speeded reaction time in both monkeys, compared with a condition where the trigger onset was not cued. The results show that neuronal responses to the trigger stimulus were less frequent and weaker when an instruction cue preceded the trigger onset than when the same trigger was presented in the absence of a previous instruction. This demonstrates decreased responsiveness in tonic striatal neurons as the monkey is switched from a condition in which the trigger onset remains largely unpredictable to one in which an instruction cue given before the trigger allows the monkey to increase his level of stimulus expectation and readiness to respond.

The instruction stimulus was also effective for eliciting a response in tonic striatal neurons. However, the percentage of neurons showing instruction responses was not as high as the fraction of neurons responding to the trigger in the uncued condition. In a number of neurons, the responses to the instruction stimulus were correlated with the disappearance of trigger responses in the cued condition.

Previous studies reported changes in the activity of tonic striatal neurons that are related to signals of behavioral significance presented in a specific context (Apicella et al. 1991, 1997). In the present study, the design of the task was such that, in the cued condition, the instruction light provided only information about the time at which the movement-triggering stimulus will be presented. In these circumstances, one can assume that the expectation of the trigger stimulus mainly reflect temporal aspects of event anticipation. Interestingly, responses to the instruction cue resemble responses to the trigger occurring in the uncued condition in terms of magnitudes of changes. This similarity might be attributable to the fact that the onset of the instruction stimulus was unpredictable in time, as was the case for the trigger in the uncued condition. This interpretation would be consistent with results from our previous study (Apicella et al. 1997) showing an increased neuronal responsiveness to a liquid reward delivered at irregular time intervals, compared with conditions in which the timing of fluid delivery was highly predictable. These data suggest that a state of expectation of meaningful sensory events is an important determinant of activity in the tonic striatal neurons.

    ACKNOWLEDGEMENTS

  We thank R. Massarino and C. Wirig for expert technical assistance.

  This work was supported by grants from the European Commission (CHRX-CT94-0463, BMH4-CT95-0608).

    FOOTNOTES

  Address for reprint requests: P. Apicella, Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.

  Received 13 April 1998; accepted in final form 6 August 1998.

    REFERENCES
Abstract
Introduction
Methods
Results
Discussion
References

0022-3077/98 $5.00 Copyright ©1998 The American Physiological Society