A multisynaptic pathway from the ventral midbrain toward spinal motoneurons in monkeys

Area of Science:

• Neuroscience
• Motor Control
• Neurobiology

Background:

• Motivation significantly enhances motor performance.
• The ventral midbrain (VM), including the ventral tegmental area (VTA), substantia nigra pars compacta (SNc), and retrorubral field (RRF), is crucial for motivation.
• The neural pathways connecting the VM to spinal motor circuits remain largely uncharacterized.

Purpose of the Study:

• To investigate the existence and characteristics of multisynaptic projections from the VM to the spinal cord.
• To elucidate the role of the VM in modulating descending motor pathways.
• To understand the neural substrate linking motivation and motor output.

Main Methods:

• Retrograde trans-synaptic labeling using a rabies virus in macaque monkeys.
• Electrical stimulation of the VM to evoke motor responses.
• Inactivation of the primary motor cortex (M1) to assess its role.

Main Results:

• Multisynaptic projections from the VM to the cervical spinal cord were identified.
• A caudorostral gradient in VM projection neuron distribution was observed, with RRF and caudal SNc being more involved.
• VM stimulation elicited contralateral forelimb muscle responses, preceded by ipsilateral M1 activity, and these responses were reduced during M1 inactivation.

Conclusions:

• A novel multisynaptic VM-spinal pathway has been identified in primates.
• This pathway is at least partially mediated by the primary motor cortex.
• The VM-spinal pathway likely plays a critical role in the modulatory control of spinal motor output, linking motivational states to motor execution.