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The Journal of Neuroscience, September 15, 2000, 20(18):7096-7108
Corticostriatal Activity in Primary Motor Cortex of the Macaque
Robert S. Turner and Mahlon R. DeLong Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
Although input from corticostriatal neurons (CSNs) plays a critical role in basal ganglia functions, little is known about CSN activity during behavior. We compared the properties of antidromically identified CSNs with those of antidromically identified neurons that project via the cerebral peduncle to distant targets. Both types of neurons were recorded in primary motor cortex (M1) of two monkeys as they performed a step-tracking task in which static loads opposed or assisted simple and precued movements of the elbow or wrist. Multiple lines of evidence suggested that CSNs and corticopeduncular neurons (CPNs) belong to distinct populations. No cells were activated from both striatum and peduncle. Compared with CPNs, CSNs had slow conduction velocities and low spontaneous rates, and the activity of most was unmodulated by sensory testing or within the tasks used. CSN activity resembled that described for M1-recipient striatal neurons: perimovement firing was small in magnitude, strongly directional, and rarely showed muscle-like load effects. Contrary to a previous report, perimovement activity in most CSNs began before movement onset. CSN activity was more selective than that of CPNs: CSN sensory responses and perimovement activities were often directionally specific, CSNs were often activated exclusively by sensory stimulation, active movement, or movement preparation, and a substantial fraction of CSNs (19%) was unresponsive to any task or manipulation. Thus, CSNs transmit signals distinct from those sent to spinal cord/brainstem. The highly selective activity of CSNs suggests that a discrete (i.e., sparse) code is used to signal cortical activation states to striatum.
Key words: primary motor cortex; basal ganglia; putamen; cerebral peduncle; arm movement; motor control; monkey; load-related activity; preparatory activity
INTRODUCTION
The massive corticostriatal projection, which directly links cortex and the basal ganglia (BG), is the major afferent to the BG and is implicated in BG-associated disorders such as Parkinson's disease (Porter et al., 1994
; Delfs et al., 1995
More generally, a study of CSN activity during behavior may ascertain whether the CS system is functionally separate from other cortical efferent systems and, if so, what factors are important in its activity. Although the large distant-projecting cells of lamina Vb are known to collateralize to the striatum in rodents (Donoghue and Kitai, 1981
Some aspects of this work have been reported previously in preliminary form (Turner and DeLong, 1993
MATERIALS AND METHODS
Animals, apparatus, and tasks. Two juvenile female monkeys (Macaca mullata, weighing 3.4 and 4.7 kg) were used in these experiments. All aspects of animal care were in accord with the Guide for the Care and Use of Laboratory Animals (National Academy Press, 1996), and all procedures were approved by the institutional animal care and use committee.
The monkeys were trained to perform a visuomotor step-tracking task to obtain juice or food rewards. We used a behavioral paradigm similar to one used in several previous studies of cortical and BG neuronal activity (Alexander, 1987
The visuomotor step-tracking task has been described in detail previously (Alexander, 1987
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Figure 1. Schematic of the behavioral task. A, Monkeys "captured" targets (white circles) presented on a computer monitor (gray rectangle) with an on-screen cursor (black square) the horizontal position of which was controlled by flexion and extension of the wrist (for monkey L) or elbow joint (as shown for monkey B). The task required two lateral cursor movements from a central start position: the first to an unpredictable target location (right or left target, 1st MOVEMENT) and the second guided by memory to the same target as captured previously (2nd MOVEMENT). Changes in target illumination and joint angle as a function of time are illustrated in B and C, respectively. Static flexing or extending torques were applied to the manipulandum starting early in the PRE-INSTRUCTION epoch of two/three of trials. D, Five epochs were used to summarize task-related neural activity for data analysis. Two epochs (PRE- and POST-INSTRUCTION) were of fixed duration and timing relative to the first and second presentation of the lateral target, respectively. The remaining three epochs (Post-Torque, 1st Mvt. and 2nd Mvt.) were of constant duration (200 msec) but their timing was fixed relative to the time of a neuron's maximal change in firing for each of the three epochs.
On two-thirds of the trials (randomly selected), a constant flexing or extending torque load (0.1 Nm) was applied to the manipulandum beginning 1-2 sec after initial capture of the center target and lasting until reward delivery (Fig. 1C). The loaded trials served three purposes: (1) to evaluate short-latency neural responses to torque perturbations, (2) to evaluate neural sensitivity to static torque during the preinstruction period, and (3) to dissociate the direction of active movement from the pattern of muscle activity used to perform the movement. When loading direction and the direction of movement were opposed, movement was performed by increasing activity in the already active agonist muscles, whereas when loading direction and movement direction were the same, movement was performed by reducing tonic postural activity in the antagonist muscles [see Alexander and Crutcher (1990)
Surgery. After training, each monkey was surgically prepared for recording using aseptic surgery under isoflurane inhalation anesthesia. A cylindrical stainless steel chamber [18 mm inner diameter (ID)] was implanted with stereotaxic guidance over a burr hole allowing access to the arm-related regions of the right M1 and the posterior putamen [centered on Horsley-Clark (HC) anterior (Ant) 10, lateral (Lat) 20, depth (Z) 20 (Winters et al., 1969
Placement of stimulating electrodes. Several days after the monkey recovered from surgery, sites for implantation of stimulating electrodes were identified using standard electrophysiological mapping techniques. Special care was taken to identify appropriate implantation sites in the putamen because of the topographic yet patchy nature of the corticostriatal innervation (Flaherty and Graybiel, 1991
1 (Winters et al., 1969
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Figure 2. Locations of chronic indwelling stimulating electrodes relative to microelectrode mapping of putamen and cerebral peduncle. The approximate location of each stimulating lead is denoted by a gray circle. Microstimulation results and somatosensory response properties of neurons encountered along recording tracks are summarized as follows: El, elbow; L, leg; M, mouth; Sh, shoulder; V, visual; Wr, wrist. Open triangle indicates the point of deepest penetration of an electrode track. Thick diagonal line indicates the portion of an electrode track where high-frequency activity characteristic of the globus pallidus was encountered. The boundaries of surrounding structures are shown for orientation: C, claustrum; Cd, caudate; GP, globus pallidus; OT, optic tract; Put, putamen; SNr, substantia nigra reticulata; STN, subthalamic nucleus; Th, thalamus. Maps were reconstructed from histological sections and microelectrode recording tracks. Data from 2 mm in the anterior/posterior dimension are collapsed onto one coronal section.
Custom-built "floating" stimulating electrodes were implanted at identified arm-related sites in putamen and the peduncle (Fig. 2, gray circles). Each electrode assembly consisted of one to three Teflon-coated PtIr microwires (each 50 µm diameter) (A-M Systems, Carlsborg, WA) fixed with cyanoacrylate glue (Loctite 420, Loctite Corp., Rocky Hill, CT) inside a short (~5 mm) length of stainless steel cannula [30 ga outer diameter, adapted from a design of Jaeger et al. (1990)
Data acquisition. Areas of M1 related to the primary joint used in the task were identified using microstimulation and sensorimotor mapping. A cortical region was determined to be "task-related" if neurons responded to active and/or passive movement of the appropriate joint and microstimulation at low currents evoked joint movement or muscle contraction (<40 microamps, 10 biphasic pulses at 300 Hz).
Microelectrode penetrations were performed throughout the task-related cortical areas while we searched for neurons activated antidromically from the putamen or peduncle stimulating electrodes. As the electrode was advanced, stimuli were delivered sequentially to each putamen and peduncle stimulating site (single
Neuronal activity was monitored while the animal performed the step-tracking task. The action potentials of single neurons were detected using a template-based spike sorting system that allowed the simultaneous discrimination of spikes from multiple neurons (Alpha Omega Engineering, Nazareth, Israel). The times of discriminated spikes were saved to disk with millisecond accuracy. For neurons that generated few spontaneous spikes, the isolation of action potentials was tested during intertrial intervals using the spikes evoked by antidromic activation. Analog data were digitized at either 200 Hz (monkey L) or 500 Hz (monkey B). The six trial types (two lateral targets × three loading conditions) were presented in random order until 10 repetitions of each trial type were collected.
After task completion, we monitored the activity of a neuron during a sensorimotor examination (Alexander and DeLong, 1985
In monkey L, EMG activity was also recorded during task performance in separate sessions after the last neural recordings. The following muscles were studied: flexor carpi ulnaris, flexor carpi radialis, flexor digitorum profundus, extensor digitorum communis, extensor digitorum VI and V, extensor carpi radialis and ulnaris, palmaris longus, abductor pollicis longus, biceps longus, brachioradialis, triceps lateralis, anterior deltoid, and latissimus dorsi.
After the last recording session, each monkey was given a lethal dose of sodium pentobarbital and was perfused transcardially with saline followed by 10% Formalin in phosphate buffer and then sucrose. The brains were blocked in place in the coronal plane, removed, cryoprotected with sucrose, cut into 50 µm sections, and stained with cresyl violet. The locations of stimulating and recording sites were reconstructed using gliosis left by electrode penetrations, the tracks left by pins inserted immediately before perfusion, and the site coordinates relative to the center of the recording chamber.
Data analysis. For each behavioral trial, spike density functions (SDFs) were constructed as the sum of Gaussian functions (unit area, 10 msec variance) centered on the times of each discriminated action potential within a trial [for method, see Szucs (1998)
Movement-related activity and the influences of movement direction and load were detected using a three-way ANOVA. The ANOVA compared the mean firing rate of a cell around the time of first movement with activity during the preinstruction period. The first factor of the ANOVA, behavioral epoch, was treated as a repeated measure (two levels: preinstruction and first movement), and the other two factors coded target direction (flexion and extension) and torque load (flexor, no-load, and extensor). A neuron was judged to have significant perimovement activity if the results of the ANOVA exceeded the threshold for statistical significance (p < 0.001) either in the main effect of epoch or in any of the interaction terms that included epoch as a factor (i.e., epoch × direction, epoch × load, or epoch × direction × load). Results of the same ANOVA were used to evaluate the influences on a neuron's perimovement activity of movement direction, torque load, and the interactions of direction and load. As in other single-unit studies using multifactor ANOVAs (Alexander and Crutcher, 1990
) was set at p < 0.001.
Preparatory activity was detected with a second three-way repeated measures ANOVA. In this case, the preinstruction and postinstruction epochs were compared as the first (repeated) factor. The remaining two factors, as before, coded target direction and torque load. A neuron was judged to have preparatory activity if the ANOVA yielded a significant main effect of epoch (p < 0.001) or significant interactions between epoch and direction and/or load. Responses to the onset of torque loads were assessed with a one-way ANOVA comparing firing rates during the post-torque epoch for the three load conditions (flexor, extensor, and no-load). Finally, the influence of loads on a neuron's tonic firing was assessed with a two-way ANOVA that compared firing rates during the preinstruction epoch for different loads and different (upcoming) target directions. As one might expect, target direction never had a significant influence on a cell's firing during the preinstruction period, so the ANOVA reduced to a one-way ANOVA with three torque levels (flexor, extensor, and no-load).
The onset times of changes in activity after torque perturbations and around movement onset were determined from peri-event SDFs (means across trials of one condition). Onsets were defined as the time at which the SDF first deviated from the preresponse control level by 2.5 SDs for >20 msec. The latency of torque responses was determined separately for each loading condition that produced a significant torque response (as determined by ANOVA; see above). The control mean and SD were taken from the 500 msec period immediately preceding torque onset. Likewise, the latencies of perimovement activity were determined for all target directions and loading conditions producing significant perimovement activity during the first movement epoch (as determined by ANOVA). Control values were from a 500 msec period immediately preceding presentation of the first lateral target. On rare occasions when the experimenter disagreed with the algorithm's estimate, onset times were corrected manually. For comparisons between populations, the earliest onset across conditions was used as a cell's latency.
An index of directional modulation (IDM) was used to compare the incidence of different patterns of directional modulation in torque responses and perimovement activity. The IDM was calculated according to the following equation: IDM = 100 × |F
5 times the magnitude of that for the opposing direction.
RESULTS
Electrode penetrations were made at 43 locations in the arm territory of the left M1 of two monkeys (Fig. 3). For more anterior electrode penetrations, neurons were included only if they were at, or posterior to, sites where microstimulation evoked arm movements at low threshold (i.e., <30 µA, 10 pulses at 300 Hz), thereby ensuring that neurons from the caudal premotor cortex were excluded (Weinrich and Wise, 1982
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Figure 3. Surface map of electrode penetrations in M1. Separate maps are shown for each of three cell types (CS, corticostriatal; CP, corticopeduncular; NA, not activated) in the two monkeys. Circle diameters indicate the number of cells of each type that were sampled at each location. The maps were derived from photographs of the cortical surface taken after perfusion, histological sections, and the chamber locations for recording tracks.
Of the 374 neurons studied during task performance, 75 were activated antidromically from the putamen (CSNs; 35 in monkey L and 40 in monkey B), and 115 were activated from peduncle stimulation (CPNs; 23 in monkey L and 92 in monkey B). Although neurons were often activated from several stimulating electrodes within the putamen or peduncle, none were activated from both the putamen and peduncle. Figure 4 shows examples of impulse collision and high-frequency following for a CSN (left) and a CPN (right). The action potentials of CSNs were typically of small amplitude and discriminable over a small range of electrode positions (<100 µm). On many occasions, action potentials were observed at a constant latency after putamen stimulation, but they were either too small or too sensitive to small shifts in electrode position for reliable spike sorting.
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Figure 4. Antidromic activation of M1 neurons from stimulating electrodes in the striatum (CS) and peduncle (CP). Antidromically elicited action potentials (*) occurred at a constant latency after stimulation ( ). Antidromic spikes collided (
) with spontaneous spikes when stimulation was delivered after a spontaneous spike at any delay shorter than the cell's antidromic latency plus the refractory period. Finally, a high-frequency (>300 Hz) train of three stimuli (
The remainder of the neurons (n = 184) were not activated antidromically (NA) but were recorded either at the same time as CS or CP recordings (n = 58) or were encountered within 0.5 mm above or below an antidromically activated neuron along the same track. Not all neurons remained well isolated, so the number of trials per condition did not always amount to 10, and the numbers of cells in a category varied for different comparisons.
Conduction velocity and spontaneous activity
In addition to the observation that no neurons were activated antidromically from both the putamen and the peduncle, other observations reinforced the view that CSNs and CPNs belong to distinct populations. The axonal conduction velocities of CSNs were considerably slower than those of CPNs (Fig. 5A). The antidromic spikes of CSNs had remarkably long latencies (range: 2.6-14.4 msec) compared with those of CPNs (range: 0.75-3.6 msec). Taking into account the estimated distances from stimulating sites in putamen and peduncle (20-25 and 31 mm, respectively), there was virtually no overlap between the conduction velocity distributions for CSNs and CPNs (Fig. 5A) (p < 0.0001, Komolgorov-Smirnov two-sample test).
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Figure 5. Distributions of basic properties for CSNs and CPNs. CSNs had slower conduction velocities than CPNs (A), lower spontaneous firing rates (B), and longer latency somatosensory responses (C) for the few CSNs that did respond to torque perturbations. (Note different ordinate scales for CS and CP distributions in C.) These differences between CSNs and CPNs were all highly significant and were consistent for the two animals studied.
The spontaneous firing rates of CSNs were markedly lower than those of most CPNs (Fig. 5B). Spontaneous rates were measured during the preinstruction epoch of nonloaded trials. During this epoch the monkey maintained a central cursor position while waiting for a lateral target to appear. CSNs seldom fired >5 spikes/sec (median rate 1.4 spikes/sec, range: 0-11 spikes/sec), whereas most CPNs exceeded 10 spikes/sec (median rate 14.8 spikes/sec, range: 0.2-38 spikes/sec; Komolgorov-Smirnov two-sample test, p < 0.0001).
Sensory responses
CSNs were also notable for their relative unresponsiveness to somatosensory stimulation and for the highly selective nature of the responses that were found. Somatosensory responsiveness was assessed in two independent ways: (1) qualitatively, by monitoring a neuron's firing during the sensorimotor examination, and (2) quantitatively, by measuring the short latency effects of load applications to the joint. Qualitatively, CPNs were more likely to respond to somatosensory exam (80/102 neurons, 78%) than CSNs (22/63 neurons, 35%;
2 = 31.2, p < 0.00001). The relative paucity of sensory responses in CSNs could not be accounted for by their low tonic firing rates. Other neuronal types with low spontaneous rates (i.e., subpopulations of CPNs and NA neurons with tonic rates <7.5 spikes/sec) responded far more frequently than CSNs to somatosensory stimulation (83 and 71% of slowly firing CPNs and NA neurons, respectively). Regardless of neuronal type, somatosensory responses were nearly always proprioceptive, as judged by their selectivity for joint rotations or, on occasion, deep probing of muscles and/or tendon taps. In monkey L, in which the wrist- and hand-related areas of M1 were explored, a small number of CSNs and CPNs (six in all) responded to light touch with distinct receptive fields on the glabrous skin of the hand. Within CS and CP populations, sensory responsive and unresponsive neurons had similar spontaneous rates and axonal conduction velocities.
For the CSNs that did respond during the sensory exam, a common feature was selectivity for specific conditions. Some neurons exhibited a discrete sensitivity to experimenter-imposed rotation of one joint in one direction. Others showed even greater selectivity by responding to rotation of one joint in one direction, but only when the arm was held in a certain posture. For example, one CSN responded only during imposed extensions of the right elbow when the animal's arm was held with the shoulder abducted and extended in the transverse plane. The neuron did not fire during elbow extensions when the shoulder was flexed in the transverse plane, nor was its activity modulated during task performance or sensorimotor examination. CP and NA neurons within 0.5 mm of this CSN responded to passive and active elbow rotations regardless of arm position. A similar degree of selectivity was found in 8 of the 22 sensory exam-responsive CSNs (36%) but never in CPNs (0/80;
A quantitative analysis of short latency torque responses further supported the view that CSNs were difficult to drive with somatosensory stimulation and that the sensory responses of CSNs were more selective than those of other neuronal populations. Cortical activity that follows a torque perturbation at short latency (<60 msec) is related to somatosensory inflow, whereas activity related to compensatory movement follows later (Evarts, 1973
The short latency torque responses of CSNs were directionally selective more frequently than those of other neurons. The seven short latency responses found for CSNs were either present for only one torque direction (e.g., for extending loads as in Fig. 6A, right panel) (n = 3) or were reciprocal with an increase in firing for one direction and a decrease for the opposite direction (Fig. 6C) (n = 4). A smaller proportion of CPNs had directionally selective responses [16% unidirectional (14/84 cells) and 43% reciprocal (36/84) (Fig. 6D),
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Figure 6. Representative short latency responses to torque perturbations for CSNs and CPNs. The torque responses of CSNs tended to be small in magnitude and either unidirectional (A) or reciprocal (C) in nature, whereas the responses of CPNs were most commonly bidirectional (B) or reciprocal (D). Mean SDFs, rasters, and overlaid traces of single trial joint angle are aligned on the onset of flexing and extending torques (vertical dotted lines in left and right subpanels, respectively). Inset figures in each panel follow the conventions of Figure 4 to illustrate antidromic activation and collision tests for the neuron that has its torque response shown.
Perimovement activity
Modulation of activity around the time of movement was much more common among CPNs than CSNs. Figure 7 illustrates a dramatic example in which we simultaneously monitored the activity of a CPN and a CSN. The CSN had a low spontaneous rate that was unmodulated around the time of movement (Fig. 7A), whereas the CPN had a large increase in firing preceding flexion movements and a reciprocal reduction preceding extensions (Fig. 7A). Perimovement changes in activity (p < 0.001, three-way ANOVA) were found in far more CPNs (96%, 110/115) than CSNs (49%, 35/72;
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Figure 7. Simultaneously recorded activity of CS and CP neurons around the time of movement. A, CSNs, as shown for this example, frequently had a low spontaneous rate that was not modulated around the time of movement (left and right subpanels show flexion and extensions movements, respectively). B, CPNs, in contrast, nearly always had significant perimovement activity. For this CPN, a marked increase in firing began ~200 msec before flexion movements (left), and a small decrease in activity was present for extensions (right). Mean SDFs (top), raster diagrams (with trials sorted according to the trigger-to-movement interval, middle), and mean angular velocity (bottom) are aligned on the time of movement onset (vertical dotted lines). In the raster diagrams, symbols along one row indicate the times of unit firing (|), target appearance ( ), and movement termination (
) for a single trial. Inset figures illustrate the antidromic activation and collision tests for the two neurons. Action potentials from the CPN are not seen in the inset in A nor are CSN action potentials seen in the B inset, because of the low spontaneous rates of both neurons.
A handful of the CSNs not activated by movement within the formal task (17%, 6/35; two not tested) became active when the animal engaged in a motor behavior with the arm free from the manipulandum. Each neuron was activated by a different behavior, but most cells fired during one or another discrete component of the Klüver board task (e.g., during finger extension into the Klüver board slot, or when bringing the hand to the mouth after retrieving a raisin). These responses were judged to be movement-related because they were consistently present across several repetitions of the activating behavior, but they were absent when the arm was moved passively through motions that imitated the activating behavior.
Among the 35/72 CSNs and 110/115 CPNs with perimovement activity, several features emerged that emphasized the similarities and differences between the two efferent populations. Figures 8 and 9 illustrate some of the features that could be found in both cell types. Perimovement modulations often began at least 100 msec before movement onset and were nearly always influenced by the direction of movement. For the examples in Figure 8, A and B, and Figure 9B, a marked increase in firing preceded extension movements but little or no change was present for flexions. For the CSN activity illustrated in Figure 9A, perimovement firing was present only for flexion movements. In some cells, torque loads influenced the magnitude of the perimovement modulation (e.g., dynamic load effects) (Fig. 8A,B) and/or the cell's tonic firing rate during the preinstruction delay period (static load effects) (Fig. 8B). The pattern of dynamic and/or static load effects often mimicked what was seen in the EMG activity of agonist muscles, such that loads opposing and assisting movement in the cell's preferred direction caused the cell to have greater and smaller changes in firing, respectively (Fig. 8A,B). Note, for the cell activity illustrated in Figure 8B, the dynamic load effect had a muscle-like activation pattern, whereas the static load effect followed a non-muscle-like pattern (i.e., preinstruction activity was elevated when loads assisted movement into the cell's preferred direction). Various non-muscle-like load effects were found for both cell types. Finally, for many cells, torque loads had no perceptible influence on perimovement phasic firing or on premovement tonic rates (Fig. 9A,B).
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Figure 8. Representative examples of "muscle-like" patterns of perimovement activity in CS and CP neurons (A and B, respectively). The perimovement firing of both cells was directional, with large increases preceding extension movements (right subpanel) and little or no change for flexions (a small increase in B and no change in A). The activity was categorized as "muscle-like" because the increase was larger when torque loads opposed extension (thick lines in SDF and top raster diagram, OPPS'D) and smaller when loads assisted extension (thin lines in SDF and bottom raster diagram, ASST'D). Movement kinematics were similar across loading conditions as can be seen by comparing the mean angular velocities for the three loading conditions (overlaid traces below raster diagrams). Separate mean SDFs and raster diagrams are shown for the three loading conditions. Otherwise, the figure follows the conventions outlined for Figure 7.
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Figure 9. Representative examples of "directional" perimovement activity in CS and CP neurons (A and B, respectively). For both neurons, perimovement activity was strongly modulated by the direction of movement but was uninfluenced by opposing or assisting torque loads (OPPOS'D and ASST'D raster diagrams, respectively), and the mean SDFs had very similar profiles for the three loading conditions (opposed, no-load, and assisted conditions denoted, respectively, by thick, medium, and thin traces overlaid at top). Other conventions follow those of previous figures.
For both CSNs and CPNs, perimovement activity often began well before the onset of movement (Figs. 8, 9, 11B). As shown in Figure 10B, more than half of the CSNs (57%, 20/35) had early movement-related activity that began within a 95% confidence range for the CPN latency distribution [65-195 msec before movement onset, calculated using a robust estimator for dispersion around the median (Rousseeuw, 1990
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Figure 10. Contrasting properties of perimovement activity in CSNs and CPNs. Compared with CPNs, the perimovement activity of CSNs was as follows: A, smaller in magnitude, and B, later in onset relative to the start of movement. C, For CSNs, perimovement activity was most commonly present for only one direction of movement (Unidir, reflected by an IDM ~100%), whereas substantial numbers of CPNs had movement-related activity that was either of the same sign for both directions (Bidir, IDM < 80%) or of opposite signs for the two directions (Recip, IDM > 120%). IDM distributions are shown in histogram form for all neurons that had significant perimovement activity. Similar differences were observed for cells sampled from monkeys L and B (denoted by hatching and gray shading, respectively).
Movement direction
For large proportions of CS and CP populations, perimovement activity was different for the two directions of movement (Table 1) (
The paucity of bidirectional activity in CSNs was confirmed with a method that avoided categorization of directionality into discrete types. Figure 10C shows the distributions of IDMs (see Materials and Methods for derivation) that were used to categorize directionality. Direct comparisons of the IDM distributions for CSNs and CPNs found a substantial difference for IDMs between 0 and 100% (i.e., for activity patterns that could possibly be classified as bidirectional; p < 0.005, Kolmogorov-Smirnov two-sample test) but no reliable difference between distributions for IDMs >100% (p = 0.43). This is consistent with the view that CSN perimovement activity (as well as that related to somatosensory stimulation, as discussed above) has a directional sensitivity that is more focused or selective for specific directions of movement than is true for CPNs or a general population of M1 cells.
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Table 1. Incidence of movement direction and torque load effects Torque loads
Effects of torque load on a cell's perimovement firing (i.e., dynamic load effects) were found in approximately half of the cells that had perimovement changes in activity, regardless of whether they were CSNs or CPNs (Table 1) (Direction/load interactions
Previous studies of the effects of movement direction and static torque on neuronal activity have classified the interactions of the two factors into three mutually exclusive categories (Evarts, 1967
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Table 2. Summary of direction/load interactions Preparatory activity
Preparatory activity, defined as increased or decreased neuronal firing during a postinstruction interval, is thought to reflect the implementation and maintenance of pretrigger aspects of a motor plan (Evarts et al., 1984
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Figure 11. Examples of "preparatory alone" and "combined" categories of preparatory activity. A, Preparatory activity in the absence of perimovement firing, like that shown in this example, was more common in CSNs than in CPNs. Tonic firing during the postinstruction period was increased for flexion trials (left) but was absent for extension trials (right). There was no change in firing related to the first or second movement (left and right vertical dotted lines) for either flexion or extension trials. B, A combination of preparatory and movement-related activity was observed in CSNs, as illustrated here. A and B show two separate epochs of unit activity (SDFs and raster diagrams) and mean velocity traces for flexion (left) and extension (right) trials. The first epoch includes the preinstruction and first movement periods, whereas the second epoch includes postinstruction and second movement periods. The SDFs reflect mean firing rates across the three loading conditions, whereas separate raster diagrams and velocity traces (overlaid below) are shown for each loading condition. In other respects, the conventions of previous figures are followed. Time scales for inset figures: A, 4 msec; B, 15 msec.
Preparatory activity was relatively rare among cells that fired at low spontaneous rates, regardless of whether they were CSNs, CPNs, or NA neurons. Preparatory activity was 2.5 times less common in CSNs than in the general population of CPNs (12/70 vs 50/114;
Selective activation of CSNs
Most CSNs (81%, 57/70) were activated by at least one of the tasks or manipulations used. Many CSNs were activated exclusively during movement preparation, active movement, or sensory stimulation, whereas very few CPNs responded to one factor alone (Table 3, Fig. 12). Preparatory activity alone (Fig. 11A) was 24 times more common among CSNs than among CPNs (Table 3, Prep alone) (
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Table 3. Segregation of preparatory activity, perimovement activity, and sensory responses
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Figure 12. Ven diagrams of the combinations of three types of activity in CSNs and CPNs. CSNs were more likely than CPNs to respond exclusively to one of the three factors: preparation to move (Mvt Prep), active movement (Active Mvt), or sensory stimulation (Sensory). A substantial fraction of CSNs (19%) were unresponsive to all factors (No Resp), whereas all CPNs were activated by at least one factor.
Compared with CPNs, CSNs were also far more likely to fire exclusively during active movement (Table 3, Mvt alone) (
DISCUSSION
The present study indicates that the motor cortex exports distinctly different messages to the striatum and spinal cord/brainstem. Not only does the primate corticostriatal projection originate from a population of neurons separate from CPNs, but the functional properties of CSNs differ from those of other M1 neurons. Relative to nearby CPNs, CSNs had slower conduction velocities, lower spontaneous rates, lower incidences of sensory responsiveness and task-related activity, and greater directional selectivity in the somatosensory and movement-related activities. The perimovement activity of CSNs was of smaller magnitude, began later on average, and seldom showed a muscle-like pattern of load effects. Finally, unlike CPNs, many CSNs exclusively signaled movement preparation, active movement or sensory stimulation. These results are consistent with a previous study of CSNs in monkey M1 (Bauswein et al., 1989
On two notable points, the present results differ from those of Bauswein et al. (1989)
Two recent studies in cats found only minor differences between CSNs and corticotectal neurons (Niida et al., 1997
Segregation of signals among M1 efferent pathways
The present results indicate that distinct signals are transmitted from M1 to the striatum and spinal cord/brainstem. Although consistent with some electrophysiological (Bauswein et al., 1989
It is quite possible that a general class of intra-telencephalic M1 efferents have firing properties similar to what we found for CSNs. It has been known for some time that neurons located outside of layer Vb tend to differ from layer Vb cells in their task-related activities (Cheney and Fetz, 1980
The distinct firing properties of CSNs and CPNs likely arise from differences in both synaptic connectivity and intrinsic properties. For instance, slowly conducting CSNs receive few thalamocortical synapses (Kitai et al., 1976
