C Locations of recorded tonically active neurons TANs plotted separately for each monkey. Each color dot represents a single neuron. TANs were recorded between 2 mm anterior A and 8 mm posterior P to the anterior commissure ac , over the lateral L and medial M extent of the striatum measured from the midline in mm.
The recording depth in mm was determined from a zero reference point as determined by using microdrive readings. The average depth of penetration of 17 mm was used to divide the precommissural striatum into dorsal and ventral regions.
Surgery was carried out under gas anesthesia isoflurane 2. We implanted a head-holding device and a recording chamber aimed to the striatum. Antibiotics and analgesics were administered after surgery. We recorded the extracellular activity of single neurons with movable glass-coated tungsten electrodes over a wide area of the anterior and posterior regions of the striatum.
Electrodes were passed inside a stainless steel guide tube 0. After penetration of the dura, the electrode was advanced toward the striatum with a manual hydraulic microdrive MO95; Narishige, Tokyo, Japan until the activity of a single neuron was isolated. Continuous monitoring of the spike waveform on a digital oscilloscope during recording allowed us to check the quality of spike isolation. Presentation of visual stimuli, delivery of reward and collection of neuronal data for off-line analyses were controlled by a computer, using custom software developed by E.
Once a neuron was isolated, we usually first examined its activity in the FRT condition. The task relationships of neuronal discharges were assessed on-line in the forms of rasters aligned on each task event. The distinctive spontaneous discharge rate and spike waveform of TANs permitted them to be easily identified in extracellular recordings from the striatum of behaving monkeys Apicella, We analyzed neuronal activity by detecting changes in TAN firing on the basis of a Wilcoxon signed-rank test Apicella et al.
The baseline firing rate was calculated during the ms preceding the presentation of the visual stimulus FRT and VRT conditions or reward URT condition , defined as the control period. A test window of ms duration was moved in steps of 10 ms, starting at the presentation of the visual stimulus or reward delivery. For each time step, we calculated the average spike counts within the interval across all trials.
The mean discharge rate in the ms window was compared, at each step, with that in the control period. The offset of a modulation was defined in the same manner by the first of at least five consecutive steps with activity back to control. We then determined the onset and offset of the modulation in the firing of the neuron with 10 ms resolution.
Magnitude of change in TAN activity was assessed by counting spikes between onset and offset of responses for each neuron showing a significant change in firing and expressed as percentage below or above baseline activity. To assess the properties of the population of TANs sampled in the different conditions, we calculated the ensemble average activity aligned with stimulus onset and reward delivery of all neurons recorded, regardless of their individual responsiveness to events.
We computed the average firing rates in 10 ms bins to identify when the population significantly changed its activity, relative to the control period ms before the first task event. End time was defined in a similar manner for the return of the ensemble average activity to that in the control period. Then durations of activity change over the population of neurons were defined on the basis of onset and offset times of these changes.
Differences in fractions of responding TANs among the testing conditions were tested with the chi-square test. Since we cannot, practically, include a large number of animals in order to satisfy the independence assumption, it should be kept in mind that we rely on standard practices in the field to make inferences about the statistical significance of our data. In addition to the quantitative assessment of task-related activities of individual TANs, we gave a description of the properties of the population of TANs by pooling activities across samples of neurons recorded in the different striatal regions.
For each neuron, a normalized perievent time histogram was obtained by dividing the content of each bin by the number of trials and the population activity was obtained by averaging all normalized histograms referenced to a particular task event.
Based on the known topographic organization of projections from the cerebral cortex and limbic system, the striatum explored in the present study was divided into a motor region, which corresponds to the part of the putamen posterior to the anterior commissure and an associative region, which predominantly includes the dorsal precommissural parts of both the caudate nucleus and putamen Parent and Hazrati, The ventral part of the caudate nucleus and putamen rostral to the anterior commissure is traditionally regarded as the limbic striatum Haber and McFarland, The approximate boundary that divides the striatum into, on the one hand, the motor striatum and, on the other hand, the associative and limbic striatum can be determined from the position of the anterior commissure.
Because no reliable anatomical or electrophysiological marker could help in defining the border between the dorsal and ventral parts of the precommissural striatum, we used recording depths to tentatively define a boundary between these two subdivisions which was situated at 17 mm which corresponds roughly to 10 mm from the dorsal border of the striatum Marche and Apicella, We recorded the activity of 62 TANs monkey F, 37; monkey T, 25 while the animals waited for the reward delivered at the end of the 1-s interval after the onset of the visual stimulus i.
We divided the striatum into three regions which correspond roughly to the functional territories conventionally defined in the primate striatum Figure 1B. As shown in Figure 1C , 26 neurons were located in the motor striatum 13 and 13 in monkeys F and T , 21 in the associative striatum 13 and 8 in monkeys F and T and 15 in the limbic striatum 11 and 4 in monkeys F and T. The mean firing frequency of TANs was similar in all three regions motor: 5. We evaluated their responsiveness to either the visual stimulus or reward in terms of a pause in TAN firing, with or without subsequent rebound activation, a very few neurons displaying a brief increase in firing before the pause.
Figure 2A summarizes the percentage of TANs responding to the visual stimulus and reward in each striatal region, separately for each monkey. Remarkably, neurons recorded in the limbic striatum 11 and 4 in monkeys F and T, respectively were invariably responsive to reward, indicating that the TAN sensitivity to reward is the strongest in this region. Figure 2. A Proportions of TANs responding to the visual stimulus and reward. Bar plots for each monkey show proportions of responses across the three striatal regions.
In each panel, a dot represents a neuronal impulse, and a line of dots represents the neuronal activity recorded during a trial. Histograms and dot displays of TAN activity are aligned on the onset of the stimulus. Vertical calibration on histograms is in spikes per second. Bin width for histograms is 10 ms. The data were taken from monkey T motor striatum, top panel and monkey F ventral striatum, middle and bottom panels. Figure 2B shows the relative proportions of the selective and nonselective response types in the three striatal regions for each animal.
It is notable that the proportion of TANs responding to both stimulus and reward was increased in the limbic striatum compared to motor and associative striatum.
On the other hand, responses that were specifically related to the stimulus were not found in the limbic striatum. The neuron shown in the top panel displayed a modulation of activity after the visual stimulus, with an excitatory component immediately before the pause-rebound response, but its discharge was not influenced by the subsequent delivery of reward.
Conversely, the neuron illustrated in the middle panel had responses to both the visual stimulus and reward, the pause-rebound response being somewhat stronger for the stimulus than for reward.
The neuron shown in the bottom panel responded selectively to reward. To further examine how recording locations influence the responsiveness of TANs, we determined the durations and magnitudes of each of the two main components of the TAN response i.
For this analysis, data from the two monkeys were pooled. Figure 3. The responsiveness of TANs to task events in distinct striatal regions. A Comparison of durations and magnitudes of the two components of TAN responses pause and rebound to the stimulus and reward across striatal regions. Magnitudes of changes are indicated as decreases pauses or increases rebounds in percentage below baseline activity. Results are pooled for the two monkeys. B Population average activity of TANs recorded in the three striatal regions.
Each curve indicates the mean activity averaged across neurons recorded in a given region for both animals as a function of time from stimulus onset left and reward delivery right. Both the responsive and nonresponsive TANs are included. As shown in Figure 3B , there was a clear modulation of the whole sample of TANs recorded in each striatal region after each task event. The population activity aligned on stimulus onset diverged significantly from that in the control period at — ms after stimulus onset for the three striatal regions and the duration of the decrease in activity i.
Therefore, the duration of the pause response to the stimulus in the limbic striatum appeared twice as long as in the motor striatum, confirming at the level of the population average that the pause response was longer in the ventral than in the dorsal striatal regions. In contrast, no differences could be observed in the duration of the increases in activity following the pause i.
Also, a significant decrease in the population activity started — ms following the delivery of reward, with durations ranging from 70 ms in the motor striatum to ms in the associative and ventral striatum. No significant increase in activity was detected, except in the limbic striatum. In summary, these results suggest a difference in TAN response features between the dorsal and ventral striatum, at the single neuron and population levels, after the reward-predicting stimulus and, to a lesser extent, after the reward itself.
We then determined whether regional-specific differences in TAN response features are influenced by changes in the length of the stimulus-reward interval. This was tested in 27 neurons 13 and 14 neurons in monkeys F and T, respectively by replacing the fixed interval FRT condition by a random interval VRT condition. The effects of the condition were assessed quantitatively by comparing durations and magnitudes of response for TANs which were responsive in both conditions.
This was done only for the pauses, because the numbers of rebound were too small to perform a similar analysis. The resulting sample included 15 and 16 neurons with pause responses to the stimulus and reward, respectively. The duration of the decrease in population activity following stimulus onset was 30, 80 and ms in the motor, associative and limbic striatum, respectively. Durations of reward responses ranged from 50 ms in the motor striatum to ms in the associative and limbic striatum.
This confirms previous findings obtained in the FRT condition that the duration of the TAN pause response was the longest in the limbic striatum. Figure 4. A Effects of a variable stimulus-reward interval on the duration and the magnitude of TAN responses to the stimulus top and reward bottom in relation to striatal region.
Same conventions as in Figure 3A. Same conventions as in Figure 3B. We used the same analysis to investigate whether the absence of the visual stimulus predictive of reward influenced regional-specific differences in TAN response to reward. We further analyzed the responsiveness of TANs by comparing the durations and magnitudes of the pause response in 21 neurons which remained responsive to reward in both conditions Figure 5A. The duration of the decrease in activity was 70, 80 and ms in the motor, associative and limbic striatum, respectively.
It therefore appears that region-specific modulations of pause response were transferred from the stimulus predictive of reward to the reward itself when passing from the FRT to the URT.
Figure 5. A Same conventions as in Figure 3A. C Response features of TANs as a function of striatal region in a sample of seven neurons tested in the three conditions. Each dot corresponds to a neuron responsive to reward and thick colored bars represent median values in different striatal regions. Finally, a total of 14 TANs were each recorded for enough time to be tested in the three conditions, seven of them being responsive to reward in all conditions 3 and 4 in monkeys F and T, respectively.
Even with this small sample size, a difference in the duration and magnitude of the pause response to reward was still visible depending on the striatal region Figure 5C , the same neurons showing stronger responses in the limbic striatum as compared to the other striatal regions.
This confirms the tendency for pause responses to be stronger in more ventrally located TANs. In summary, the pause response of TANs was stronger, in terms of duration and magnitude, in the limbic striatum compared to the other striatal regions, suggesting that differences in the functional properties of TANs may exist between the dorsal and ventral regions of the striatum. Previous single-neuron recording studies in the striatum of behaving monkeys have established that TANs are prominently involved in the signaling and learning of motivational significance of stimuli Apicella, Most of these studies have emphasized the constancy of response properties of TANs in the dorsal parts of the caudate nucleus and putamen, indicating that these neurons emit a signal that is uniformly distributed in the motor and associative regions of the primate striatum.
On the other hand, no studies have been carried out in the ventral part of the striatum, also referred to as the limbic striatum, a region considered closely implicated in reward processing.
The present study documents, for the first time in the monkey, the response properties of TANs located within the ventral striatum. Although we found TANs responsive to rewarding stimuli in all striatal regions explored, there were more frequent in ventral than in dorsal striatum. In addition, the duration of the typical pause response of TANs and, to a lesser extent, its magnitude were enhanced in the ventral striatum compared to the dorsal striatum.
We found that both individual TANs and the population as a whole showed different degrees of responsiveness to rewarding stimuli according to their location in dorsal or ventral regions of the striatum.
Although the exact borders of the ventral striatum cannot be unambiguously delineated by electrophysiological recording, the caudal border of this region was operationally defined, as in our earlier study Marche and Apicella, , by the anterior commissure which serves as an anatomical landmark separating the anterior and posterior striatum in the primate. Ventral TANs that we sampled were located rostral to the anterior commissure and included the most ventral part of both the caudate nucleus and putamen based on depth readings on the microdrive.
As many studies have shown, we report that the dominant response of TANs to rewarding stimuli consisted of a pause in firing, often followed by a rebound activation. Of these two consecutive response components, the pause was more influenced by the recording site, being particularly strong in the ventral striatum in terms of duration and magnitude.
However, despite the lack of statistically significant results in the present study, the rebound activation following the pause response to either the visual stimulus or reward tended to be more pronounced in the ventral striatum compared to the dorsal striatum.
It therefore seems that both early and late response components of ventral TANs showed a trend toward being larger than those of the dorsal TANs.
This heterogeneity in response features of TANs raises the possibility that cholinergic interneurons do not carry signals with homogeneous properties to dorsal and ventral striatal output pathways. A few studies in behaving rodents have examined the activity of TANs in dorsal and ventral striatal regions. Although information on the neurons classified as TANs in rodents is not always in agreement with that collected in monkeys, some variation in TAN response properties has been observed between striatal regions Yarom and Cohen, In particular, in rats trained to perform a nose-poke task, Benhamou et al.
Interestingly, these authors also noticed that pauses in firing in response to task events were approximately twice as long in the ventral striatum as in the dorsolateral striatum, an effect that is similar to the one described here in monkeys. In other words, it is located at the anterior side of the head. Thus, this is the difference between dorsal and ventral. While dorsal structures are located in the opposite direction to the stomach, ventral structures are located in the direction of the stomach.
Hence, this is another difference between dorsal and ventral. Moreover, dolphins and sharks have dorsal fins while the pelvic fins of fish are ventral. In other words, dorsal structures are located in the opposite direction to the stomach while ventral structures are located at the side of the stomach.
The carapace of a crab is its dorsal side while a bee has its wings on the dorsal side. The carapace of a crab, shell of a turtle, back side of the human do not bear external appendages, whereas bees and other insects have developed extensions such as wings from their dorsal side.
The dorsal side is termed as the Dorsum, which is the area where the backbone is present in vertebrates. However, the term dorsal can be used to refer a relative location of an organ or a system in the body of an animal. As an example, oesophagus of vertebrates is dorsal to their heart. Additionally, the lateral line of a fish can be found dorsally to the pectoral fin. The term dorsal is also used as an adjective, especially in the fishes. The topmost fin of a fish is known as the dorsal fin.
However, head of the human is not considered as a dorsal organ despite it lies at the topmost location of the body.
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