Rethinking the brain’s wiring diagram

Image credit: Caroline Davis2010. (

Appearances can be deceiving. When looking at the outmost layer of the brain, called the neocortex, it looks like a simple sheet of neurons. But the truth is far from it. This “simple sheet” has a complex sub organization of its own. And not only that, the neocortex is the brain structure that endows us with advanced cognitive abilities, such as thought and language.

Leopoldo Petreanu, principal investigator at the Champalimaud Centre for the Unknown, is working on cracking the wiring diagram of the neocortex. “The neocortex is actually a complex network. It is composed of six layers of neurons, which are connected in an intricate manner. By mapping out these connections, we hope to understand how this seemingly simple brain area is capable of performing such remarkable functions.”

How does one go about mapping these connections? Petreanu decided to do it by following the wires. “Communication between neurons is done through a part of the neuron called the axon, which functions as a long ‘wire’ that connects neurons both locally and across different brain areas. We hypothesised that there might be a special relation between the neurons that individual axons connect to. We asked: if two neurons connect to the same axon, will they also be connected to each other?”

To answer this question, Petreanu has deviced a groundbreaking method. “To understand how this network functions,” he explains, “we developed a novel technique that allows us to identify groups of neighboring neurons that single axons connect to. Specifically, we focused on axons that communicate visual information from a brain structure called the thalamus to the primary visual area of the neocortex.”

Using this technique, in a study published in the journal Nature Neuroscience, Petreanu and his team presented a map of neural connections over long distances in the brain, thereby providing an unprecedented view of the neocortex’s wiring diagram that challenges the current one.

The new diagram

Until now, the wiring diagram of the neocortex said that the processing of visual information happens in a serial manner: most visual information arrives from the thalamus directly to one specific layer, called L4. Then, it is thought that the neurons at L4 process the information and relay it to another layer called L2/3 for further processing.

But that’s not what the researchers now saw. In fact, they discovered that the processing is not serial, it’s parallel: “we found that when an L4 neuron and an L2/3 neuron were interconnected, the thalamic axon ‘branched off’, forming one independent connection with the neuron in L4 and one with the neuron in L2/3.”

“That’s our main finding. We identified the existence of these connections which ‘skip a layer’. This way, neurons in L2/3 not only receive processed visual inputs from L4, but also ‘raw data’ from the thalamus. This parallel processing may enable L2/3 cells to specialise in the detection of visual features, such as particular arrangement of edges in visual scenes.”

Another important finding in the study revealed yet another level of interconnectivity within the neocortex: when two L4 neurons were connected to each other, then the same thalamic axon would also connect to both of them.

This discovery suggested a special role for L4 neurons. “It had been hypothesised that L4 neurons act as amplifiers of certain features of the visual signal, such as enhancing the edges of visual objects. Our results support this hypothesis; pairs of interconnected L4 neurons are constantly signaling back and forth between themselves. This interconnectivity, combined with a common thalamic input, it is a mechanism that could generate an amplifying effect in these circuits.”

These observations not only answered Petreanu’s question, but have also made a significant impact on the field. “This new diagram changes the way we understand how the brain processes information. We found that connections in the neocortex have exquisite specificity: single axons arriving from distant brain areas selectively target groups of neurons that are in turn also connected with each other. By continuing to dissect these circuits, we are hoping to one day fully understand how the brain is capable of creating an internal representation of the outside world.” He concludes.




Liad Hollender works as a Science Writer at the Science Communication Office at Champalimaud Research



Edited by: Ana Gerschenfeld & Catarina Ramos(Science Communication office).; Image by: Caroline Davis2010. Link to image.



Loading Likes...