In a study published in Nature Communications, XU Ninglong’s lab at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences identified a pathway from the premotor cortex to the superior colliculus (SC) that is critical during memory-guided decisions, and dissected the neural circuit mechanisms underlying motor planning.
To survive in a dynamically changing world, animals should not always respond to the sensory stimuli reflexively. Instead, they should sometimes hold sensory information in memory, plan an action, and implement the action at an appropriate future time. How does the brain plan future actions? Which brain regions and circuits are critical?
A previous study showed that the anterior lateral motor cortex (M2) is an important cortical substrate for motor planning. Several follow-up studies implicated a variety of subcortical brain regions downstream of M2 in motor planning such as basal ganglia. These interconnected brain regions form a complex motor planning network. But the circuit logic in this network is far from clear. To understand brain-wide circuit mechanisms underlying motor planning, one needs to take a pathway- and cell-type-specific approach.
The researchers from XU’s lab conducted anterograde tracing from M2. They found dense projections in the lateral SC, a midbrain structure previously implicated in planning and executing eye movements in primates, and that the SC also receives basal ganglia input and is important for voluntary drinking. Based on these anatomical tracing data and past literature, they hypothesized that the pathway from M2 to SC may play a critical role during motor planning.
To test this hypothesis, the researchers established a parametric behavior paradigm in mice. A motor planning period was formed which gaps sensation and action. Delay lengths and perceptual difficulties were varied across trials, allowing the researchers to test the precise role of the circuit during motor planning with different memory demands.
Based on results from optogenetic inactivation during different behavior epochs and brain regions, the researchers found that both M2 and SC play an important role during motor planning. Simultaneous inactivation of both brain regions caused larger effect than inactivation of M2 alone, indicating that SC does not passively relay M2 information, but actively and additionally contributes to motor planning.
These inactivation experiments inspired them to further ask what kind of task-related information is sent from M2 to SC. Therefore, the researchers retrogradely labelled M2 neurons that project to SC and performed in vivo two-photon calcium imaging of these projection-based M2 neurons during mice’s performance.
Compared with randomly labeled neurons in M2, cells projecting to SC showed stronger choice information coding and this choice information was progressively more selective for the contralateral action as the trial unfolds. These results supported that M2-SC circuit carries motor planning information. But are these signals causal for behavior?
The researchers then conducted chemogenetic manipulation experiments and specifically inactivated the M2-SC circuit without influencing other M2 downstream. They found that M2-SC inactivation selectively impaired mice’s performance on trials with long delays and higher perceptual difficulty. These results supported the causal role of M2-SC circuit for motor planning and decision maintenance.
To test how SC local circuits further process choice information from M2, the researchers compared neural activities of SC excitatory and inhibitory neurons during the task.
They found that both SC cell types receive M2 input, so they may both further process information from M2 and contribute to motor planning. Using fiber photometry, they found that while excitatory neurons encode choice information consistently during sound and delay periods, potentially helping to maintain task information, inhibitory neurons showed more dynamic and heterogeneous choice coding, likely playing modulatory roles within the SC.
This study systematically investigated a circuit from premotor cortex to a subcortical collicular region for motor planning, and it provides insights to the circuit mechanisms underlying motor planning.
XU Ninglong
Center for Excellence in Brain Science and Intelligence Technology
E-mail: xunl@ion.ac.cn
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