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REPORT
1Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut; and 2Department of Physiology, Shiga University of Medical Science, Ohtsu, Shiga, Japan
Submitted 7 October 2003; accepted in final form 29 July 2004
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ABSTRACT |
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INTRODUCTION |
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, 2004a, b; Tanibuchi and Goldman-Rakic 2003; Watanabe and Funahashi 2004), whereas two others described a great deal of mid- and postsaccadic activity in and adjacent to the internal medullary lamina (IML) including the ventral lateral nucleus (VL) and the ventral posterior lateral nucleus (VPL), lateral to the MD (Schlag and Schlag-Rey 1984; Schlag-Rey and Schlag 1984; Wyder et al. 2003, 2004). This suggests that saccade-related neurons are organized along a medial-lateral axis; neurons within and lateral to the IML, to which we refer as "intralaminar" and "paralaminar" thalamic neurons, respectively, seem to begin their saccade-related activity later than neurons in the MD. One major goal of the present study was to directly test this hypothesis by comparing paralaminar and MD thalamic neurons in the same monkeys and tasks. Second, because we had found neurons in the MD that exhibited saccade-related activity exclusively during memory-guided saccades, a further objective was to examine if the paralaminar thalamus also contained such neurons. Third, we had also found picture-selective activity in the MD (Tanibuchi and Goldman-Rakic 2003); therefore we additionally examined whether neurons in the paralaminar thalamus had such activity. |
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METHODS |
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Two rhesus monkeys (Macaca mulatta, male, 9.0–11.0 kg) that served as subjects in this study were the same as in our previous study (Tanibuchi and Goldman-Rakic 2003). We recorded from the left hemisphere in each animal. All procedures in the training, surgery, recording, and housing of the monkeys were carried out in accordance with the Yale University Animal Care and Use Committee and National Institutes of Health Guidelines.
Experimental procedures
The surgical, training, and analytic procedures employed in this study were as described in our previous report (Tanibuchi and Goldman-Rakic 2003). Monkeys were tested with an oculomotor delayed-response (ODR) task and a visually guided saccade (VGS) task, both of which involved central fixation and peripheral target presentation at eight randomly interleaved locations (13° eccentricity, 45° angular separation), and a picture fixation (PICT) task that involved only central fixation.
ODR TASK. In the ODR task, each trial was initiated by the monkey fixating on the central target for 0.5 s, whereupon the visual cue was presented at one of the eight peripheral locations for 0.2 s. The animal was required to maintain fixation on the fixation point throughout sequential task epochs: 0.5-s fixation period, 0.2-s cue presentation period, and 3.0-s delay period. The fixation point disappeared at the end of the delay, instructing the monkey to make a saccade to the remembered location within 0.5 s after the disappearance of the fixation target.
VGS TASK. The monkey looked at the fixation point and maintained fixation for 1.0 s. The fixation point disappeared and, simultaneously, the visual cue appeared at one of the eight peripheral locations for 0.5 s. The monkey made a sensory-guided saccade to the peripheral cue within 0.5 s.
PICT TASK.
The monkey was required to maintain fixation throughout all task epochs, which included, in sequence, central fixation (0.5 s), pictorial (faces or objects) stimulation (1.0 s), and post stimulus fixation (0.5 s). See Tanibuchi and Goldman-Rakic (2003) for examples of the pictures that we used.
While monkeys performed the preceding tasks, we recorded single-neuron activity with either tungsten or Elgiloy microelectrodes aimed at the paralaminar thalamic nuclei. The on-line computer system sampled neuronal and ocular position signals and stored these data in relation to task events. To analyze data in the ODR task, average firing rates during four epochs (cue, delay, pre, and post) were tested for significant modulation by ANOVA as previously described (Tanibuchi and Goldman-Rakic 2003). This was followed by a statistical comparison of the activity in each epoch against the firing rate in a 1.0 s intertrial interval (ITI). The cue epoch was 0.5 s long and began at cue onset; the delay epoch extended from the end of the cue epoch until the offset of the fixation point; the pre epoch was the 0.25-s period leading up to saccade initiation; and the post epoch was the 0.5-s period after saccade initiation. A neuron was considered to have saccade-related activity if the firing rate in either the pre or post epochs (or both) significantly exceeded that during the ITI. Data in the VGS task were analyzed similarly; firing rates in pre- and postsaccadic epochs (0.2 and 0.5 s, respectively) were also compared with the ITI activity, but we set 0.2 s rather than 0.25 s as the presaccadic period to avoid counting any visual response as a presaccadic response. In the PICT task, each trial was divided into four time windows: fix, phasic, tonic, and post. The fix period started 0.1 s after the initiation of the fixation target and lasted for 0.4 s, the phasic epoch began at the onset of the pictorial presentation and lasted for 0.2 s, the tonic period spanned 1.0 s throughout stimulus presentation, and the post epoch began at stimulus offset and lasted for 2.0 s. A repeated-measures two-way ANOVA (P < 0.05) was applied to each neuron with stimulus and time window as factors; specific comparisons were made between firing rates in each of the four periods (fix, phasic, tonic, and post) and the 1.0-s ITI. Neurons showing a significant main effect of stimulus or a significant interaction between stimulus and time window at a level of P < 0.05 were considered selectively responsive (see O'Scalaidhe et al. 1999 for details).
To study the saccade-related activity in finer temporal detail, we analyzed the exact onset times of the presaccadic bursts. Onset time was determined for the neuron's preferred target direction using the method of MacPherson and Aldridge (1979). Each action potential record was replaced with a Gaussian function (SD = 15 ms) to produce continuous spike density functions (SDFs). The mean ± SD of the SDF, determined during 1–2 s before the initiation of saccades, established a 95% confidence interval. The burst onset time was defined as the midpoint between the first intersection of the corresponding SDFs with the upper (or lower) limit of the confidence interval and the first peak of responses that were sustained for 
0.1 s beyond the confidence interval (Tanibuchi and Goldman-Rakic 2003). We classified a neuron as having a pre-, mid-, or postsaccadic burst of saccade-related activity if the burst started before saccade initiation, during the saccade, or after saccade termination, respectively.
The spatial selectivity of saccade-related neurons was quantitatively analyzed by the Gaussian curve method (Bruce and Goldberg 1985). Tuning curves were obtained by determining the parameters of the Gaussian function that best fit (least 
2) the mean firing rates of these neurons for eight cue directions (see Chafee and Goldman-Rakic (1998) for details). Sometimes we observed cue-, delay-, or saccade-related responses that were omni-directional. Because omni-directional responses might be related to reward, or expectancy of reward, we further examined the relationship between firing rate and reward delivery for such neurons in a qualitative way by pausing the task and manually delivering rewards in predictable or unpredictable schedules.
Reconstruction of recording sites
Records of anterior-posterior (A-P), medial-lateral (M-L) and dorsal-ventral (D-V) coordinates of recording sites were kept for all neurons and used, along with iron deposits on specific electrode tracks, to reconstruct a composite map of recording sites based on Olszewski (1952).
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RESULTS |
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We examined each of our 163 paralaminar thalamic neurons in at least one saccadic task and, if time permitted, the PICT task (Table 1). One hundred forty seven were tested with the ODR task (Table 1, row 1), and 21% (n = 31) exhibited significant event-related changes in firing rate (ANOVA, P < 0.05). The proportions of neurons having activity related to various ODR task events were similar to what we had found in the MD (Fig. 2A) (Tanibuchi and Goldman-Rakic 2003). As in the MD, paralaminar thalamic neurons with purely saccadic activity (61%) far exceeded those active only during the cue (13%), only during the delay (7%) or during more than one epoch (cue, delay, saccade; 19%). Also similar to the MD, most of these neurons with saccade-related activity (alone or in combination with other types of activity, n = 23) exhibited spatial tuning (87%, n = 20; 14 contralateral, 6 ipsilateral), whereas the remainder (13%, n = 3) were omni-directional. We tested the omni-directional neurons to see if they were firing in relation to the reward (see METHODS), but none were.
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Activity in the PICT task
Of 128 neurons recorded during the PICT task, four (3%) were weakly but significantly activated by particular pictures of faces/objects (Table 1, row 3). This proportion was much lower (2 test, P < 0.005) than what we had found previously in MD thalamus (16/115 = 14%) (Tanibuchi and Goldman-Rakic 2003). All 128 neurons also were tested in the saccadic tasks, but none of the 4 PICT-responsive neurons was modulated in those tasks.
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DISCUSSION |
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). We found that neuronal activity in both regions was similar except for later saccade-related bursts of activity in the paralaminar thalamus. Our second goal was to see if a substantial proportion of neurons in the paralaminar thalamus, as in the MD thalamus, fired specifically for memory-guided saccades; this was indeed the case. Finally, we searched for picture-related modulation of activity in paralaminar thalamus. We only found a few neurons with such activity, but these neurons were not active in the oculomotor tasks, suggesting a dissociation similar to what we had seen in the MD thalamus. In sum, this report and our prior one using identical monkeys and methods (Tanibuchi and Goldman-Rakic 2003) firmly establish some notable similarities and differences in the properties of neurons as one proceeds from medial to lateral in the thalamus. General properties of paralaminar versus MD neurons
We found that some neurons in the paralaminar thalamus were active in oculomotor tasks, exhibiting cue-, delay-, and highly prevalent saccade-related activity, as had been found previously in the MD (Sommer and Wurtz 2002, 2004a, b; Tanibuchi and Goldman-Rakic 2003; Watanabe and Funahashi 2004), in the dorsolateral prefrontal cortex (Chafee and Goldman-Rakic 1998), and in the thalamic region in and around the IML (Wyder et al. 2003, 2004). As we had described in the MD (Tanibuchi and Goldman-Rakic 2003), saccade-related neurons in the paralaminar thalamus were mostly spatially tuned, in agreement with prior reports of neurons near this region (Schlag-Rey and Schlag 1984; Wyder et al. 2003).
An intriguing difference between neurons in paralaminar versus MD thalamus was in the timing of saccade-related bursts of activity. Whereas presaccadic bursts of activity predominated in the MD, mid- and postsaccadic bursts were more common in the paralaminar thalamus (Fig. 2B). Most of this mid- and postsaccadic activity was spatially tuned. We will discuss these mid- and postsaccadic bursts of activity further in the following text.
ODR-task specificity of mid- and postsaccadic bursts
As in the MD thalamus (Tanibuchi and Goldman-Rakic 2003), about half (9/20 = 45%) of saccade-related neurons in the paralaminar thalamus had saccade-related activity only during the ODR task. A previous study (Wyder et al. 2003) showed that saccade-related activity near the paralaminar thalamus can be different for memory-guided versus visually guided saccades but that report found only neurons that fired specifically for visually guided saccades. In contrast, in our sample neurons were just as likely to fire specifically for memory-guided saccades. This difference between studies may be due to probing slightly different thalamic regions.
Taking together two of our results—that paralaminar thalamic neurons typically have mid- and postsaccadic bursts and that these are often specific for memory-guided saccades—we suggest that many of these neurons play a feedback role in spatial working memory. This is consistent with a general hypothesis that has been emerging concerning the motor-related signals that ascend through the thalamus (Sommer and Wurtz 2002, 2004a, b; Tanibuchi and Goldman-Rakic 2003; Wyder et al. 2003). We know, for example, that some MD neurons relay presaccadic activity from the superior colliculus up to the FEF that may be a corollary discharge signal (i.e., a copy of the descending motor commands; Sommer and Wurtz 2002, 2004a, b). The predominantly mid- and postsaccadic activity recorded in and around the IML by us and previous investigators (Schlag and Schlag-Rey 1984; Schlag-Rey and Schlag 1984; Wyder et al. 2003) may represent a different type of feedback signal, one that follows saccade initiation. In particular, the ODR-exclusive mid- and postsaccadic activity that we found may serve to "reset" the sustained activities of prefrontal neurons engaged in spatial working memory, i.e., erase the memory information of the correct spatial location once each trial is successfully completed (as proposed by Funahashi et al. 1991).
One limitation of our study should be noted: we only used targets at 13° eccentricity. We did this so that we could directly compare the present results with our prior findings in the MD thalamus (also obtained using 13° eccentricity stimuli). Note that because we used exactly the same methods to study both paralaminar and MD thalamus, the striking difference in saccadic burst onset times found in the two structures (Fig. 2B) is highly likely to reflect an inherent difference in the neurons in these two parts of thalamus. However, there is a possibility (which seems very remote to us) that the receptive/movement fields of the paralaminar neurons were less centered at 13° on average than were those of the MD neurons, and because saccadic bursts can be delayed near the edges of movement fields in structures such as the superior colliculus (Sparks et al. 1976), this could have trivially caused later bursts in the paralaminar neurons. In general, using other eccentricities might have revealed additional properties of paralaminar thalamic (and MD) neurons. Further work will be needed to characterize these neurons' receptive, memory, and movement fields in finer detail.
Neuronal activity while viewing pictures
We found only a few paralaminar thalamic neurons that responded selectively to the pictures of faces and objects. None of these were responsive in oculomotor tasks. Thus, as in the MD thalamus and the prefrontal cortex (see Tanibuchi and Goldman-Rakic 2003), it appears that the object- and spatial-coding properties of paralaminar thalamic neurons are largely dissociable.
Because primates usually perform object identification in their central visual field (e.g., Freedman et al. 2001; Wilson et al. 1993), we presented our pictorial stimuli at the fovea. However, to further test the dissociation of object- and spatial-coding properties of paralaminar thalamic neurons, in future studies, pictorial stimuli should also be presented peripherally where neurons may have optimal activity during the oculomotor tasks.
Position of the paralaminar thalamus in the visuosaccadic system
This report and our prior one (Tanibuchi and Goldman-Rakic 2003) evaluated and directly compared neurons in the paralaminar and MD thalamus, and yet much more work is needed before we might understand the role of these structures in primate behavior. The challenge of the work ahead can be appreciated by considering the connectional anatomy of this region, which is dominated by complicated loops (for reviews, see Schlag-Rey and Schlag 1989; Sommer 2003). For example, the dorsolateral prefrontal cortex sends efferents via the pontine nuclei to the cerebellar cortex, which projects to the cerebellar nuclei. In turn, efferents from the cerebellar nuclei target the medial part of the caudal VLc where neurons project to the prefrontal cortex (Leiner et al. 1991; Middleton and Strick 2001; Schmahmann and Pandya 1997a, b). Also, the posterior parietal cortex (Andersen et al. 1985; Chafee and Goldman-Rakic 1998; Gnadt et al. 1988) sends signals through subcortical circuits that eventually terminate, via paralaminar thalamus, in the dorsolateral prefrontal cortex (Middleton and Strick 2001). Paralaminar thalamic neurons thus may play a role in cortico-cortical communications and perhaps in thalamo-thalamic interactions as well: presaccadic responses in the MD thalamus, for example, could potentially enter a transsynaptic pathway, e.g., an MD-prefronto-parieto-thalamic route, to eventually modulate paralaminar thalamic neurons (Cavada and Goldman-Rakic 1989; Goldman-Rakic and Porrino 1985; Kievit and Kuypers 1977; Leichnetz 2001; Leichnetz and Gonzalo-Ruiz 1996; Selemon and Goldman-Rakic 1988; Taktakishvili et al. 2002; Yeterian and Pandya 1985). In sum, the paralaminar thalamus is part of an extensive web of circuits. Further study of its signals has the potential to offer new insights into the widespread systems that mediate visual, cognitive, and oculomotor behavior.
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GRANTS |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Address for reprint requests and other correspondence: I. Tanibuchi, Dept. of Physiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Ohtsu, Shiga 520-2192, Japan (E-mail: buchi{at}belle.shiga-med.ac.jp)
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ABSTRACT
INTRODUCTION
