Dopamine control of pyramidal neuron activity in the primary motor cortex via D2 receptors

AbstractDopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate how DA, through the activation of D2 receptors (D2R), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in layer V of M1. Our data reveal a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.Significance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.

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Partial Reconstruction of Muscle Activity From a Pruned Network of Diverse Motor Cortex Neurons

Journal of Neurophysiology ◽

10.1152/jn.00544.2006 ◽

2007 ◽

Vol 97 (1) ◽

pp. 70-82 ◽

Cited By ~ 29

Author(s):

Marc H. Schieber ◽

Gil Rivlis

Keyword(s):

Motor Cortex ◽

Motor Neurons ◽

Primary Motor Cortex ◽

Activity Patterns ◽

Neuron Activity ◽

Emg Activity ◽

Weighted Sum ◽

Partial Reconstruction ◽

Average Similarity ◽

Upper Motor Neurons

Primary motor cortex (M1) neurons traditionally have been viewed as “upper motor neurons” that directly drive spinal motoneuron pools, particularly during finger movements. We used spike-triggered averages (SpikeTAs) of electromyographic (EMG) activity to select M1 neurons whose spikes signaled the arrival of input in motoneuron pools, and examined the degree of similarity between the activity patterns of these M1 neurons and their target muscles during 12 individuated finger and wrist movements. Neuron–EMG similarity generally was low. Similarity was unrelated to the strength of the SpikeTA effect, to whether the effect was pure versus synchrony, or to the number of muscles influenced by the neuron. Nevertheless, the sum of M1 neuron activity patterns, each weighted by the sign and strength of its SpikeTA effect, could be more similar to the EMG than the average similarity of individual neurons. Significant correlations between the weighted sum of M1 neuron activity patterns and EMG were obtained in six of 17 muscles, but showed R2 values ranging from only 0.26 to 0.42. These observations suggest that additional factors—including inputs from sources other than M1 and nonlinear summation of inputs to motoneuron pools—also contributed substantially to EMG activity patterns. Furthermore, although each of these M1 neurons produced SpikeTA effects with a significant peak or trough 6–16 ms after the triggering spike, shifting the weighted sum of neuron activity to lead the EMG by 40–60 ms increased their similarity, suggesting that the influence of M1 neurons that produce SpikeTA effects includes substantial synaptic integration that in part may reach the motoneuron pools over less-direct pathways.

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Cue to action processing in motor cortex populations

Journal of Neurophysiology ◽

10.1152/jn.00274.2013 ◽

2014 ◽

Vol 111 (2) ◽

pp. 441-453 ◽

Cited By ~ 18

Author(s):

Naveen G. Rao ◽

John P. Donoghue

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Visual Target ◽

Neuron Activity ◽

Action Processing ◽

Action Network ◽

Ensemble Activity ◽

Array Recordings ◽

Population Decoding ◽

Single Neuron Activity

The primary motor cortex (MI) commands motor output after kinematics are planned from goals, thought to occur in a larger premotor network. However, there is a growing body of evidence that MI is involved in processes beyond action generation, and neuronal subpopulations may perform computations related to cue-to-action processing. From multielectrode array recordings in awake behaving Macaca mulatta monkeys, our results suggest that early MI ensemble activity during goal-directed reaches is driven by target information when cues are closely linked in time to action. Single-neuron activity spanned cue presentation to movement, with the earliest responses temporally aligned to cue and the later responses better aligned to arm movements. Population decoding revealed that MI's coding of cue direction evolved temporally, likely going from cue to action generation. We confirmed that a portion of MI activity is related to visual target processing by showing changes in MI activity related to the extinguishing of a continuously pursued visual target. These findings support a view that MI is an integral part of a cue-to-action network for immediate responses to environmental stimuli.

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Dynamics of Single Neuron Activity in Monkey Primary Motor Cortex Related to Sensorimotor Transformation

Journal of Neuroscience ◽

10.1523/jneurosci.17-06-02227.1997 ◽

1997 ◽

Vol 17 (6) ◽

pp. 2227-2246 ◽

Cited By ~ 89

Author(s):

Jun Zhang ◽

Alexa Riehle ◽

Jean Requin ◽

Sylvan Kornblum

Keyword(s):

Motor Cortex ◽

Single Neuron ◽

Primary Motor Cortex ◽

Neuron Activity ◽

Sensorimotor Transformation ◽

Single Neuron Activity

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Skill Representation in the Primary Motor Cortex After Long-Term Practice

Journal of Neurophysiology ◽

10.1152/jn.00784.2006 ◽

2007 ◽

Vol 97 (2) ◽

pp. 1819-1832 ◽

Cited By ~ 97

Author(s):

Yoshiya Matsuzaka ◽

Nathalie Picard ◽

Peter L. Strick

Keyword(s):

Motor Cortex ◽

Motor Skills ◽

Primary Motor Cortex ◽

Functional Organization ◽

Response Times ◽

Internal Representation ◽

Neuron Activity ◽

Movement Sequences ◽

A Site

The acquisition of motor skills can lead to profound changes in the functional organization of the primary motor cortex (M1). For example, performance of movement sequences after prolonged practice is associated with an expansion of the effector representation in M1. Paradoxically, there is little evidence that the activity of M1 neurons reflects acquired skills, especially sequences of movements. We examined the activity of M1 neurons during skilled movement sequences in macaques trained to successively hit targets on a monitor. The targets appeared either pseudorandomly (Random mode) or in one of two repeating sequences (Repeating mode). With practice, response times for repeating sequences substantially declined and the monkeys performed the task predictively. Highly trained animals retained the acquired skill after long gaps in practice. After >2 yr of training, 40% of M1 neurons were differentially active during the two task modes. Variations in movement kinematics did not fully explain the task-dependent modulation of neuron activity. Differentially active neurons were more strongly influenced by task mode than by kinematics. Our results suggest that practice sculpts the response properties of M1 neurons. M1 may be a site of storage for the internal representation of skilled sequential movements.

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