How do specialized regions develop in the brain?

A recent study led by the Allen Institute for Brain Science has advanced our understanding of how the brain’s specialized regions develop their unique functions. 

By employing a cutting-edge method called BARseq to extensively map neurons across nine mouse brains, the experts provided unique insights into the brain’s cellular landscape.

Specialized subregions of the brain

“The vertebrate brain is organized into subregions that are specialized in function and distinct in cytoarchitecture and connectivity. This spatial specialization of function and structure is established by developmental processes involving intrinsic genetic programs and/or external signaling,” wrote the study authors. 

“Although gene expression can change during cell maturation and remains dynamic in response to internal cellular conditions and external stimuli, a core transcriptional program that maintains cellular identity usually remains steady in mature neurons.” 

“Thus, resolving the expression of core sets of genes that distinguish different types of neuron provides insight into the functional and structural specialization of neurons.”

Unique cellular signatures of specialized brain regions

The team discovered that while different brain regions contain similar types of neurons, each region possesses a distinct combination of these cells, effectively giving each area a unique cellular “signature.” This finding is a significant step forward in understanding the complex organization of the brain.

Additionally, the study explored how the absence of sensory inputs, such as sight, affects these cellular signatures. “BARseq lets us see with unprecedented precision how sensory inputs affect brain development. These broad changes illustrate how important vision is in shaping our brains, even at the most basic level,” said co-lead author Xiaoyin Chen, an Assistant Investigator at the Allen Institute. 

Sensory inputs and brain development

The researchers found that mice deprived of sight experienced a significant reorganization of cell types within the visual cortex, which blurred the distinctions with neighboring areas. This reorganization was observed across half of the cortical regions, although to a lesser extent.

BARseq, which stands out for its efficiency and cost-effectiveness, enables the tagging of individual brain cells with unique RNA “barcodes.” This allows for tracking connections across the brain and analyzing gene expression to identify large numbers of neurons in tissue slices. “BARseq lets us see with unprecedented precision how sensory inputs affect brain development,” Chen elaborated.

Mapping millions of brain cells

Study co-leader Mara Rue, a scientist at the Allen Institute, highlighted the advantages of BARseq over other mapping technologies. “Previously, capturing single-cell data across multiple brains was challenging,” she said. Fortunately, BARseq simplifies this process, making it more accessible for a broader range of researchers.

In just three weeks, the researchers were able to map more than 9 million cells from eight brains, demonstrating the method’s rapid capabilities. “BARseq allows us to move beyond mapping what a ‘model’ or ‘standard’ brain looks like and start to use it as a tool to understand how brains change and vary,” Chen explained. “With this throughput, we can now ask these questions in a very systematic way, something unthinkable with other techniques.”

Broader study implications 

Both Chen and Rue hope that making the BARseq method freely available will encourage its use across the scientific community, allowing more researchers to explore the brain’s organizational principles or delve into cell types associated with diseases. 

“This isn’t something that only the big labs can do. Our study is a proof of principle that BARseq allows a wide range of people in the field to use spatial transcriptomics to answer their own questions.”

More about specialized brain regions

The human brain is an incredibly complex organ composed of various specialized regions, each responsible for different functions. 

Frontal lobes 

The frontal lobes, positioned at the front of the brain, are crucial for cognitive functions like decision-making, problem-solving, and controlling behavior and emotions. 

Parietal lobes

The parietal lobes, located in the middle section of the brain, play essential roles in processing sensory information and helping with spatial orientation and manipulation.

Temporal lobes

The temporal lobes, found on the sides of the brain, are key for processing auditory information and are also critically involved in memory storage. Meanwhile, the occipital lobes at the back of the brain are primarily responsible for visual processing, interpreting everything we see.

Cerebellum 

In addition to these lobes, the cerebellum, situated beneath the rear portion of the cerebrum, is vital for motor control and coordination. The brainstem, connecting the brain to the spinal cord, governs many automatic functions necessary for survival, such as breathing, heart rate, and blood pressure.

More specialized areas

Furthermore, within these larger regions are more specialized areas, like Broca’s area in the frontal lobe, crucial for speech production, and Wernicke’s area in the temporal lobe, important for understanding language. The hippocampus, deeply embedded in the temporal lobe, is essential for forming new memories.

Each of these regions works in concert with the others, forming a highly interconnected and dynamic network that enables everything from simple reflexes to complex thought processes.

The research is published in the journal Nature.

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