Category: Research

A new interdisciplinary study by researchers from the Ruth and Bruce Rappaport Faculty of Medicine and the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering at the Technion reveals a surprising insight: local release of dopamine—a molecule best known for its role in the brain’s reward system—is a key factor in acquiring new motor skills

From writing and typing to playing a musical instrument or mastering a sport, learning movement-based tasks is one of the brain’s most complex challenges. This collaborative new study reveals how the brain reorganizes its neural networks during such skill learning and uncovers the vital role of dopamine in this process of motor learning.

The research, published in Nature Communications, was led by Dr. Hadas Benisty, Prof. Jackie Schiller, and M.D./Ph.D. student Amir Ghanayim, with contributions from Prof. Ronen Talmon and student Avigail Cohen-Rimon from the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering.

The ability to acquire new motor skills is fundamental for adapting to our environment. This learning takes place in the primary motor cortex—a region of the brain responsible for planning and executing voluntary movements. From this cortical “command center,” signals are sent via the spinal cord to activate muscles and coordinate movement. Neural activity in this region is known to change as we learn new skills. However, the mechanisms that drive these changes remain unclear.

Key findings of the study

The researchers used advanced calcium imaging in behaving mice and chemogenetic inhibition techniques—engineered receptors and specific drugs—to temporarily switch off targeted brain cells, allowing researchers to study their function. They mapped dynamic changes in neural networks with cellular resolution within the motor cortex during the acquisition of a motor skill, and discovered that during learning, neural networks transition from a “beginner” to an “expert” structure.

Crucially, this process depends on the local release of dopamine in the motor cortex. Under normal conditions, dopamine molecules are delivered to this region by neurons originating in the ventral tegmental area (VTA)—a central dopamine hub in the brain. The researchers hypothesized that this dopamine release triggers plasticity mechanisms, leading to changes in functional connectivity between neurons in the motor cortex. This process enables motor learning by storing new skills for future use. In essence, this is a form of reinforcement learning, where successful movement outcomes reinforce the brain’s internal wiring.

What happens when dopamine is blocked?

To test the necessity of this mechanism, the researchers examined both the activity and functional connectivity of the neural network and the learning process when dopamine release in the primary motor area was blocked. The results were clear: When dopamine was blocked, learning stopped completely—mice were unable to improve their performance in a forelimb-reaching task. The motor cortex neural network remained static. However, as soon as dopamine release was restored, learning resumed, along with reorganization of the neural network.

The study provides compelling evidence that local dopamine release serves as a crucial signal for neural plasticity in the motor cortex, enabling the necessary adaptations for producing precise and efficient motor commands. A particularly interesting discovery was that blocking dopamine did not affect previously learned motor skills. In other words, the researchers proved that dopamine is essential for learning new movements but is not required for performing already learned ones.

This study represents another step toward understanding brain plasticity and learning mechanisms at the cellular and network levels. It highlights the brain’s ability to reorganize itself, allowing us to refine our motor skills throughout life. These insights may also have important implications for treating neurological disorders such as Parkinson’s disease, where dopamine production is impaired, and motor learning is compromised.

Is there a difference in brain structure between men and women? If we were to find such a difference in a single neuron, would it matter?

One of the most useful models for studying these questions is the nematode Caenorhabditis elegans (C. elegans). This tiny worm has several characteristics that make it an excellent research model, one of which is that every cell in its body has a predetermined identity and lineage.

Like humans, C. elegans has two sexes. However, instead of male and female, the two sexes of this worm are male and hermaphrodite—a self-fertilizing individual capable of producing both male and female gametes (sperm and eggs), allowing it to reproduce without a partner.

Researchers from the Faculty of Biology at the Technion-Israel Institute of Technology have examined these sex-specific differences (sexual dimorphism) in C. elegans, and uncovered surprising findings.

The study, published in Proceedings of the National Academy of Sciences, was led by Dr. Yael Iosilevskii and Dr. Menachem Katz from Prof. Beni Podbilewicz’s Lab, in collaboration with Prof. David H. Hall of the Albert Einstein College of Medicine in New York.

The researchers discovered that a highly branched neuron called PVD, previously characterized in hermaphrodites, forms a different structure in males. Moreover, while in hermaphrodites, PVD functions primarily in pain sensing, in males, it has an additional role during mating; when its development is disrupted, males are slower and less coordinated. This discovery provides a unique example of sexual dimorphism in the structure of a single neuron, which is linked to behavioral differences.

‘Male’ vs. ‘female’ brains

It has long been established that men and women have different susceptibilities to various neurological disorders. For example, women are more prone to depression, while men have a higher risk of Parkinson’s disease. Could these differences be linked to the structure of individual neurons in the brain? This is difficult to determine due to the sheer number of neurons in the human brain—approximately 75 billion.

Even if a difference were found between the sexes in just one neuron, pinpointing its exact contribution would be challenging, as even the simplest tasks require a multitude of intricately interconnected neurons.

To explore the significance of a single neuron’s spatial structure, researchers have turned to the nematode C. elegans, just one millimeter long. A unique feature of this organism is that the identity of all 302 neurons in the hermaphrodite is invariant, allowing scientists to map their placement, spatial structure, and connections fully.

“Furthermore,” said Prof. Podbilewicz, “within the nematode population, there are also male individuals with distinct anatomy, additional neurons, and different behavior. This makes for a remarkably simple system where we can directly ask: What determines the structure of each neuron in the nervous system? Are there sex-specific differences, and do they affect behaviour?”

To answer these questions, Dr. Iosilevskii and Dr. Katz studied the development of the sensory neuron PVD. This neuron has a highly branched structure, with repetitive subunits resembling a candelabra (“menorahs”). Its distinctive shape and its development during the organism’s maturation have made it a research focus for over a decade. While much is known about its development in hermaphrodites, PVD had not been characterized in males or examined for sexual dimorphism.

The Technion researchers set out to determine whether male PVD neurons develop a different spatial structure and whether this difference influences a male’s behavior.

When examining PVD development in males, the researchers found that its menorah-like structures remained consistent across both sexes. However, they were surprised to discover that in adult males, PVD extends additional branches into the tail fan—a specialised male organ used for mating. Along with Prof. Hall, they found that these branches are entirely separate from the previously known neurons in this region.

This unique branching of PVD does not occur during the tail fan’s development but emerges immediately afterward, during the final molt from juvenile to adult. Shortly afterwards, the male begins to exhibit his sex-specific mating behavior. The researchers further discovered that when PVD does not develop properly, this mating behavior is impaired, causing males to become slower and less coordinated.

This discovery of sexual dimorphism in the structure of a single sensory neuron, which also relates to male-specific behaviour, provides a unique example in C. elegans and opens new avenues for studying sex-based neural differences. The discovery is expected to enhance our understanding of how such sexual dimorphisms alter responses both at the single-cell level and the behaviour of the whole organism.