Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex - PubMed (original) (raw)

Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex

Nandakumar S Narayanan et al. Neuron. 2006.

Abstract

Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding.

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Figures

Figure 1

Figure 1

(A) Sequence of events in the delayed-response task. Rats pressed a lever for 1000 ms (delay period) and released the lever within 600 ms of the onset of an auditory trigger stimulus (Correct responses) presented at the end of the delay period. Two types of errors occurred in the task. Premature errors occurred if the lever was released before the trigger stimulus. Late errors occurred if the reaction time was greater than 600 ms.

Figure 2

Figure 2

(A) Percentage of neurons with significant press, delay, and release activity among neuronal ensembles recorded from dmPFC. Example of single neurons modulated around (B) press, (C) delay, and (D) release. Rasters aligned to lever release. Gray regions indicate temporal epochs used to assess the statistical significance of event-related modulation of firing rate. In (B), modulation was assessed using rasters aligned to lever press. Rasters are sorted by lever press duration with long lever presses at the top.

Figure 3

Figure 3

Examples of neurons that fired differently on correct trials (green) and on premature error trials (gray). (A) Neuron that predicted correct trials (IAB = 0.21 bits) better than premature errors (IAB = 0.16 bits). (B) Neuron that predicted premature errors (IAB = 0.24 bits) better than correct trials (IAB = 0.10 bits). Gray regions indicate temporal epochs analyzed with statistical classifiers. (C) Neurons in dmPFC predict premature errors (mean ± SEM) significantly better than correct trials. Asterisk indicates significance (p < 0.005).

Figure 4

Figure 4

(A) Percentage of premature errors in six rats during preoperative behavior, in control sessions (with saline infused into dmPFC; blue), in sessions with dmPFC inactivated via muscimol (red), and in recovery sessions (green). Asterisk indicates significance (p < 0.005). (B) Kernel density estimates of the distribution of lever press duration (from press to release) for all responses in control sessions (blue) and in sessions with dmPFC inactivated (red). (C) Lever force data revealed that rats exerted similar levels of force on the lever with and without dmPFC inactivated. (D) Video data suggests that dmPFC inactivation does not change motor behavior (See supplementary videos).

Figure 5

Figure 5

(A) Percentage of neurons with significant press, delay, and release activity in control sessions (blue), in sessions with dmPFC inactivated (red), and in recovery sessions (green). Example of single neurons modulated by (B) press, (C) delay, and (D) release in control sessions (blue) and in sessions with dmPFC inactivated. Rasters aligned to lever release. Gray regions indicate temporal epochs used to assess the statistical significance of event-related modulation of firing rate. In (B), modulation was assessed using rasters aligned to lever press. (E) Normalized peri-event histograms for all neurons recorded in control sessions (left panel) and sessions with dmPFC inactivated (right panel). The order of neurons is sorted by firing rate during the delay period. The top two-thirds of motor cortical neurons fired at reduced rates in sessions with dmPFC inactivated as compared to control sessions. Asterisk indicates significance (p <0.005).

Figure 6

Figure 6

(A) Functional coupling during the delay period is apparent in simultaneously recorded pairs of neurons in dmPFC (vertical axis) and motor cortex (horizontal axis). This pair is initially positively correlated and then becomes negatively correlated as the rat waits to respond (diagonal axis). Spikes from the dmPFC neuron led those from the motor cortical neuron by −50 ms. (B) Another pair of neurons in dmPFC and motor cortex with delay-related functional coupling. This pair is negatively correlated early in the delay period and then becomes positively correlated. Importantly, in this example functional coupling exists despite the weak modulation of the dmPFC neuron during the trial.

Figure 7

Figure 7

Percentage of neuronal pairs with significant functional coupling around press, delay, and release epochs. Asterisk indicates that more neuronal pairs with significant JPSTH correlations were found than expected by chance (p < 0.005).

Figure 8

Figure 8

During delayed-response performance, activity in motor cortex (blue) is prominently modulated during lever press, delay, and lever release. While animals are holding down the lever and waiting to respond, delay-related activity in motor cortex is influenced by top-down control from dmPFC (red) in order to inhibit temporally inappropriate responses.

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