Be it when grabbing a cup of coffee or painting the intricate strokes on the Monalisa, our brain orchestrates movements of our hand with remarkable precision. These skilled movements require timely coordination between multiple brain regions, including the motor cortex, cerebellum and basal ganglia. A recently published study in Cell Reports by Anupama Sathyamurthy, who heads a neuroscience lab at IISc; and her team, has identified a previously unknown role of the SC in forelimb control. 

The SC is a region in the midbrain located just above our brainstem. Traditionally, it has been known to direct goal-oriented movements of the head and the eyes, such as turning the head toward a sound or focusing the eyes on a moving object. A key feature that enables this function is its ability to seamlessly integrate information from multiple sensory modalities, including vision and proprioception. This allows the brain to create a clear representation of the goal (moving object, for example) in relation to our body, and then direct the relevant body part (eye or head) towards the goal.

Sathyamurthy and her group, who are interested in understanding how the brain controls skilled forelimb movement, reasoned that this unique property of the SC may make it indispensable for directing goal-oriented movements not only of the head and the eyes, but also the forelimb. Surprisingly, little was known about the SC’s involvement in the forelimb movement, prompting them to investigate its role.

To explore this, they leveraged cutting-edge genetic techniques in mice to selectively silence a specific population of SC neurons and examine its effects on reaching. Since mice naturally use their tongues to drink water, they developed an automated training protocol to encourage them to reach for water droplets instead. Using machine learning algorithms to track forelimb movements, they precisely measured reach accuracy.

The team found that silencing excitatory neurons in the SC impaired the mice’s ability to reach for the water droplets. However, these reach deficits were unlikely to be due to an inability to sense the droplet, as the mice were still able to adjust their arm movements when the waterspout was moved up or down, even though they continued to miss the target. Sathyamurthy explains that this suggests ​“the SC is actively involved in transforming sensory information into motor output.” 

Neural circuits do not function in isolation, and the SC works in tandem with other brain regions to refine movement. The study found that disrupting signals from the substantia nigra pars reticulata, a basal ganglia region involved in movement regulation, to the SC, similarly impaired the mice’s ability to reach, highlighting the importance of this connection in maintaining reach accuracy. Interestingly, the researchers also discovered direct inputs from the cerebellum to the SC, an underexplored neural pathway, whose function remains to be understood.

Abhilasha Joshi, Assistant Professor at the National Centre for Biological Sciences (NCBS), Bangalore, an expert in locomotion and movement, emphasises that the study showcases extensive and detailed behavioural observations with precise circuit manipulations. Joshi adds, ​“These findings offer valuable insights into the neural basis of reaching movements in rodents.”

The SC, once thought to be primarily responsible for eye and head movement coordination, is emerging as a crucial hub for skilled forelimb control. This discovery reshapes our understanding of how the brain executes precise movements and highlights the intricate interplay between different neural circuits. 

Understanding how the SC contributes to the movement has profound implications. Patients with Balint’s syndrome suffer from difficulties in reaching for objects through visual cues, similar to the deficits observed in this study, adds Sathyamurthy. 

Joshi adds that a great addition to the study would be combining their circuit-level approach with large-scale electrophysiology to understand the neural coding of computations performed by individual neurons and what these sensory-motor mismatch assessment signals might look like.

Beyond medicine, these insights could aid the development of advanced robotic limbs and prosthetic devices. 

By mimicking how the SC integrates sensory information to guide movement, engineers could design more efficient control systems for artificial limbs, helping individuals with motor impairments.