Different modulation of common motor information in rat primary and secondary motor cortices

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Abstract

Rodents have primary and secondary motor cortices that are involved in the execution of voluntary movements via their direct and parallel projections to the spinal cord. However, it is unclear whether the rodent secondary motor cortex has any motor function distinct from the primary motor cortex to properly control voluntary movements. In the present study, we quantitatively examined neuronal activity in the caudal forelimb area (CFA) of the primary motor cortex and rostral forelimb area (RFA) of the secondary motor cortex in head-fixed rats performing forelimb movements (pushing, holding, and pulling a lever). We found virtually no major differences between CFA and RFA neurons, regardless of neuron subtypes, not only in their basal spiking properties but also in the time-course, amplitude, and direction preference of their functional activation for simple forelimb movements. However, the RFA neurons, as compared with the CFA neurons, showed obviously a greater susceptibility of their functional activation to an alteration in a behavioral situation, a 'rewarding' response that leads to reward or a 'consummatory' response that follows reward water, which might be accompanied by some internal adaptations without affecting the motor outputs. Our results suggest that, although the CFA and RFA neurons commonly process fundamental motor information to properly control forelimb movements, the RFA neurons may be functionally differentiated to integrate motor information with internal state information for an adaptation to goal-directed behaviors. © 2014 Saiki et al.

Figures

  • Figure 1. Behavioral task performance. A) A schematic of the forelimb movement task and recording sites for the two motor cortices. Rats held (for 1 s) and pulled a spout-lever to acquire reward water in a head-fixed condition. Multineuronal activity was recorded from the caudal and rostral forelimb areas (CFA and RFA) [primary and secondary motor cortices (M1 and M2), respectively] during task performance. Upper right: electrode tracks (arrowheads; layer 5) for the CFA and RFA recordings in Nissl-stained sections. See Materials and Methods for details. B) Lever trajectory and electromyogram (EMG) activity in right forelimb. Top: lever and EMG traces for several trials. Bottom: averaged EMG power aligned with the end of push or the onset of pull movements (vertical lines). C) Behavioral task performance. Top: hold time until the lever pull onset in response to cue tone presentation after the hold period (1 s) in a rat. Black and gray colors indicate correct and error trial responses, respectively. Bottom: peak distribution of hold time in all of the rats. doi:10.1371/journal.pone.0098662.g001
  • Figure 2. Basal spiking properties of CFA and RFA neurons. A) Classification of isolated units in CFA (orange) and RFA (green) into regularspiking (RS; spike duration .0.5 ms, light colors) and fast-spiking (FS; #0.5 ms, dark colors) subtypes of neurons. Top: ongoing (all averaged) spike rate plotted against spike duration for individual neurons. Bottom: bimodal distribution of spike duration. Insets, typical spike waveforms for the two neuron subtypes (mean 6 s.d.; calibration: 1 ms, 0.1 mV; gray bar, spike duration). B) Coefficient of variation (CV) of inter-spike intervals (ISIs) in CFA and RFA neurons. Histograms show CV distributions for RS (light) and FS (dark) subtypes. C) Cumulative probability analysis of the CV distribution shown in B. D) Temporal feature in auto-correlogram (ACG) in CFA and RFA neurons. We defined ACG bias as a median value in ACG from 0 to + 100 ms (red lines in two insets). Histograms show ACG bias distributions for RS (light) and FS (dark) subtypes. E) Cumulative probability analysis of the ACG bias distribution shown in D. doi:10.1371/journal.pone.0098662.g002
  • Figure 3. Time-course of functional activity in CFA and RFA neurons. A) An example of a neuron (CFA-FS) showing functional (task-related) activity. Spike activity was first aligned with the onset (0 s) of pull movements and then averaged in correct (left) and false start (right) trials. Black and red dots in raster plots represent spikes and cue onsets, respectively, in consecutive trials (correct, 20 trials; false start, 12 trials). Note the similar activity irrespective of cue presentation. B) Definition of task-related activity. The number of spikes during correct trials was plotted against task relevance (p in KS test, assuming a uniform distribution) for individual neurons (pull-aligned analysis). Black and gray dots represent the task-related ($40 trials, $50 spikes, and p,161026) and non-task-related (discarded) neurons, respectively. Insets illustrate two (poorly and well) task-related activities in the plot. C) Definition of Hold-, Push-, and Pull-type activities by peak position in push- and pull-aligned analyses. D,E) Functional activity
  • Figure 4. Direction preference of Push-/Pull-type activity in CFA and RFA neurons. A) Relative spike rate during forelimb movement in an opposite direction (pull for push, and visa versa) in Push- (left) and Pull-type (right) groups of RS (upper) and FS (lower) subtypes in each area. In Pushtype groups, spike rate was first normalized with the peak activity during push movements in individual neurons, and then, they were sorted by the amplitude of relative spike rate for pull movements (large to small). Pull-type groups were analyzed in a similar way. In this analysis, neurons were included in both Push- and Pull-type groups if they showed significant Push-type activity as well as Pull-type activity. B) Spike-rate changes in the Push- and Pull-type groups of RS and FS subtypes (orange, CFA; green, RFA; triangles, RS; circles, FS). Averaged spike rate during push or pull movements (SRPUSH, SRPULL) was plotted against baseline spike rate in the lever hold period (SRHOLD) for individual neurons (left and middle in each group). Cumulative probability analysis (right) shows the distribution of direction preference index [DPI: (SRPULL 2 SRPUSH)/(SRPULL + SRPUSH)] in the CFA and RFA neurons. doi:10.1371/journal.pone.0098662.g004
  • Figure 5. Different modulation of Hold- and Pull-type activities in CFA and RFA neurons. A) Intentional (original) and incidental pull movements in a Go/No-go response task. In Go trials, rats must pull the spout-lever deliberately and quickly in response to the presentation of original Go cue to win a reward (Int. pull; ’intentional pull’ as a rewarding response). In No-go trials, the rats must keep holding the spout-lever during an extended hold period [1.0–1.6 s after the presentation of No-go (extension) cue]. After the correct No-go response, the rats were allowed to pull the spout-lever to lick the reward anytime (Inci. pull; ’incidental pull’ as a consummatory response). Note that the same amount of reward was delivered in both trial types, but more effortful processing would be required for intentional (original) pull movements in the Go trials. B) Left: averaged lever trajectories (mean 6 s.d. traces, aligned with the pull onset) for intentional (pink) and incidental (purple) pull movements in one rat (top) and in all of the 38 sessions (24 rats; bottom). Right: distribution of reaction time for intentional pulls (pink; from Go cue onset to pull onset) and incidental pulls (purple; from reward-pumping noise to pull onset) in one rat (top) and all of the rats (bottom; latency to peak). C) Functional activity aligned with the onset (0 s) of intentional pull in Go trials (1st column from the left), of the No-go cue (2nd) and of incidental pull (3rd) in No-go trials, in RS (top) and FS (bottom) subtypes of the CFA (left) and RFA (right) neurons. The spike activity that was significant in the first column (Int. pullaligned in Go trials) was normalized across the three columns by the peak amplitude from the first column for the individual neurons, which were sorted by the peak time position in the first column (e.g., CFA-RS neurons 1–181). Below, the activity that was significant only in the No-go trials was normalized and sorted by the peak in the third (Inci. pull-aligned) column (e.g., CFA-RS neurons 1–34). Rectangles indicate time windows for Hold- (a, a’, c, c’) and Pull-type (b, b’, d, d’) activities for comparisons between Go and No-go trials. An asterisk indicates Pre-pull-type activity, which was in between the Hold- and Pull-type activities (see Fig. 6C). doi:10.1371/journal.pone.0098662.g005
  • Figure 6. Large reduction in Hold-type activity by an extension of the hold period in RFA-RS neurons. A) Populational changes in normalized spike rate in the Hold-type groups (significant in Go trials) of CFA-RS (orange) and RFA-RS (green) neurons [mean 6 s.e.m. traces, aligned with the onset (0 s) of intentional pull in Go trials (left), No-go cue (middle), and incidental pull (right) in No-go trials]. Horizontal bars (a and a’) correspond to the time windows shown in Fig. 5C. Note that the Hold-type activity of RFA-RS was lower than that of CFA-RS neurons in the No-go trials (a’), and also that no change was observed in response to the No-go cue presentation. B) Left: averaged spike rates of Hold-type activity (significant in Go trials) before intentional pull (SRGo HOLD, corresponding to Fig. 5C, a) and before incidental pull (SRNo-go HOLD, corresponding to a’) for individual CFA-RS (orange, filled triangles) and RFA-RS neurons (green). Open triangles represent those with statistical significance only in No-go trials (corresponding to Fig. 5C, c’ and c). Right: cumulative probability analysis of the distribution of normalized spike rates during an extended hold period in No-go trials (a’) in CFA-RS and RFA-RS neurons. There was a larger reduction in the Hold-type activity in RFA-RS neurons in the extended period than that in CFA-RS neurons. C) Populational changes in normalized spike rate in Pre-pull-type groups of CFA-RS (orange; as indicated by an asterisk in Fig. 5C) and RFA-RS (green) neurons [mean 6 s.e.m. traces, aligned with the onset (0 s) of Go or No-go cue (left, for Go and No-go trials, respectively) and incidental pull (right, for No-go trials)]. A horizontal bar indicates a range of intentional pulls. These types of neurons abruptly stopped a gradually increasing spike activity just prior to intentional/incidental pull movements. doi:10.1371/journal.pone.0098662.g006
  • Figure 7. Large amplitude changes in Pull-type activity for intentional and incidental pulls in RFA-RS neurons. A) Populational changes in normalized spike rate in the Pull-type groups (significant in Go trials) of CFA-RS (orange) and RFA-RS (green) neurons [mean 6 s.e.m. traces, aligned with the onset (0 s) of intentional pull in Go trials (left), the No-go cue (middle), and incidental pull (right) in No-go trials]. Horizontal bars (b and b’) correspond to the time windows shown in Fig. 5C. Vertical error bars indicate s.d. values for CFA-RS (orange) and RFA-RS (green) neurons. Note that RFA-RS neurons showed a larger s.d. value during incidental pulls than CFA-RS neurons, and also that no change was observed in response to the No-go cue presentation. B) Left: averaged spike rates of Pull-type activity (significant in Go trials) during intentional pulls (SRGo PULL, corresponding to Fig. 5C, b) and during incidental pulls (SRNo-go PULL, corresponding to b’) for individual CFA-RS (orange, filled triangles) and RFA-RS neurons (green). Open triangles represent those with statistical significance only in the No-go trials (corresponding to Fig. 5C, d’ and d). Middle: relative Pull-type activity that was normalized with the baseline spike rate (SRGo HOLD) in the same neurons that are shown in the left. Right: cumulative probability analysis of the distribution of normalized spike rates during incidental pulls (b’) in the CFA-RS and RFA-RS neurons. The Pulltype activity of RFA-RS neurons was increased or decreased more extensively than that of CFA-RS neurons. Arrowheads indicate representative neurons that were simultaneously recorded from CFA (orange) or from RFA (green). C) Left: larger Pull-type activity changes were found in the RFA-RS neurons than in the CFA-RS neurons across varying extended hold periods [1.0–1.6 s from the No-go (extension) cue to reward delivery]. Right: Pulltype activities in two representative neurons for CFA (a) and RFA (b), indicated by polylines in the left panel. doi:10.1371/journal.pone.0098662.g007
  • Figure 8. A hypothetical model. Our schematic model of different motor functions of the primary and secondary motor cortices (M1 and M2) in voluntary movement control. See Discussion for details. doi:10.1371/journal.pone.0098662.g008

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Saiki, A., Kimura, R., Samura, T., Fujiwara-Tsukamoto, Y., Sakai, Y., & Isomura, Y. (2014). Different modulation of common motor information in rat primary and secondary motor cortices. PLoS ONE, 9(6). https://doi.org/10.1371/journal.pone.0098662

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