New brain map reveals neuron connections behind motor function

Movement is a complex process governed by a network of neuronal circuits spread across multiple regions of the nervous system. These regions, including the cortex, basal ganglia, brainstem, and cerebellum, form a collaborative system that selects and refines movements.

These supraspinal structures send information to the spinal cord, which acts as the final relay in translating motor commands into precise muscle actions. Despite years of research, much remains to be understood about how descending motor pathways interact with spinal circuits to control motor output.

The journey of motor signals starts in the brain and ends in the spinal cord, where motor neurons control muscle contractions. However, most of these signals pass through interneurons, specialized cells within the spinal cord. These interneurons act as intermediaries, interpreting and modifying the commands from the brain before they reach motor neurons.

Over the years, researchers have identified multiple descending motor pathways, such as the corticospinal, rubrospinal, and reticulospinal tracts.

Published in the journal, Cell Press, these pathways coordinate various movements, including posture adjustments, limb control, and locomotion. Yet, understanding the specific targets of these pathways within the spinal cord has proven challenging.

A breakthrough in recent years has been the classification of spinal interneurons into eleven distinct groups, each with unique molecular and developmental characteristics.

In the ventral spinal cord, four classes, known as V0 to V3 interneurons, have emerged as crucial components for locomotion and skilled movements. Among these, V1 interneurons play a significant role in shaping motor behavior.

V1 interneurons, which express the transcription factor En1, are inhibitory neurons that regulate motor output. Studies have shown that disrupting their activity slows rhythmic locomotor patterns and causes abnormal limb movements. These findings emphasize their critical role in motor control.

Using advanced techniques like genetically modified viruses and three-dimensional brain mapping, scientists have traced connections between the brain and V1 interneurons in the cervical spinal cord. This approach revealed a network of over 26 brain regions that send direct inputs to these interneurons.

These regions include the medulla, pons, midbrain, cerebellum, and cortex. Interestingly, while the input from these regions is broad, it also shows biases toward specific subsets of V1 interneurons.

The researchers focused on two molecularly defined subsets of V1 interneurons: those expressing the transcription factors Foxp2 and Pou6f2. These subsets exhibit distinct connectivity patterns, suggesting that different brain regions may preferentially target specific interneuron groups to execute precise motor functions.

To map these connections, researchers used a genetically modified rabies virus to trace neuronal pathways. The virus, engineered to jump only one synapse, was fluorescently tagged, allowing scientists to track its progression. By targeting V1 interneurons, they pinpointed brain regions responsible for sending motor signals to these cells.

The team then employed serial two-photon tomography to create a high-resolution, three-dimensional atlas of the brain's connections to the spinal cord. This technology slices the brain into hundreds of micron-thick sections, revealing fluorescently labeled neurons.

The resulting map not only highlighted the origins of signals reaching V1 interneurons but also provided a detailed framework for studying the interactions between brain and spinal circuits.

This comprehensive atlas, now available as an interactive online tool, is a valuable resource for researchers investigating motor control. It offers a hypothesis-generating platform, enabling scientists to predict how specific brain regions influence spinal motor circuits and motor behavior.

The findings represent a significant step in unraveling the complexity of motor control. As Jay Bikoff, PhD, from St. Jude Children’s Research Hospital, explained, motor neurons in the spinal cord are not isolated entities.

Their activity is shaped by networks of diverse interneurons. Understanding how these networks interact with descending motor pathways is key to deciphering the neural basis of movement.

While much progress has been made, the diversity of interneurons presents ongoing challenges. Each class of interneurons is highly heterogeneous, with multiple subtypes that integrate sensory and motor inputs.

Some interneurons, for example, selectively process signals based on the behavioral state, such as walking or reaching. This state-dependent gating highlights the complexity of the spinal cord's integrative role.

Moreover, the study underscores the importance of modularity in spinal circuits. Certain interneurons appear to be dedicated to specific motor functions, such as controlling limb movements or maintaining posture. This modularity may explain how the nervous system achieves the precision and adaptability needed for diverse motor behaviors.

The three-dimensional atlas of V1 interneurons is more than just a static representation of connections. It offers a dynamic resource for understanding how the brain communicates with the spinal cord. By providing insights into the anatomical and functional organization of motor pathways, it sets the stage for future research aimed at linking brain activity with behavior.

Anand Kulkarni, PhD, one of the study’s authors, likened the task of mapping these pathways to untangling a ball of Christmas lights, a feat made even more challenging by the evolutionary complexity of the nervous system. Yet, with tools like the brain atlas, researchers are better equipped to tackle these challenges.

The study’s implications extend beyond basic science. By shedding light on the circuits underlying motor control, it may inform the development of therapies for neurological conditions that impair movement. Disorders such as spinal cord injuries, Parkinson’s disease, and ALS could benefit from a deeper understanding of these pathways.

As Bikoff noted, the data from this research allow scientists to make new predictions about motor control. By investigating how specific brain regions connect to spinal circuits, researchers can uncover the mechanisms that drive movement and behavior.

This knowledge could pave the way for novel interventions that restore motor function in patients with neurological disorders.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

Like these kind of feel good stories? Get The Brighter Side of News' newsletter.