Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - InterWiring (Wiring up the SomatoSensory Cortex)

Teaser

The development of sensory processing is fundamental for proper and accurate representation of the environment as animals transition into actively interacting with it. Even though environmental stimuli may be identical throughout life, they way the brain reacts to them changes...

Summary

The development of sensory processing is fundamental for proper and accurate representation of the environment as animals transition into actively interacting with it. Even though environmental stimuli may be identical throughout life, they way the brain reacts to them changes extremely with age. This makes sense since there is an ever-increasing necessity to extract more information from the environment for a more elaborate behavioral response. Understanding the structural changes in the brain that allow for specific functional changes to take place is of fundamental importance not only for the healthy brain, but also for disorders in which the developmental milestones are not reached. This project is aimed at untangling how a set of key inhibitory cells that act as a counterpart and regulator of the more numerous excitatory ones, start engaging in brain activity during development. As the second largest population of cells in the brain, inhibitory neurons play an essential role in brain function. Very simply put, without them we cannot survive.

Work performed

Using newly built imaging and computational methods we have managed to visualize and analyze comprehensively how three main groups of inhibitory cells that reside close to the surface of the brain connect to other excitatory and inhibitory neurons within and across their resident area, and also assess how their connectivity changes across age. These anatomical findings have allowed us to have a window into how these cells would respond to environmental stimuli and specifically touch events coming from the mouse’s facial hair. We subsequently directly tested their functional activation and revealed significant and intriguing alterations over time. Overall these findings identify a novel window of developmental structural and functional rearrangements in the mouse cortex that defines its engagement in higher order brain computations. In addition, we have made headway into some of the molecules that are involved in the way these cells establish their connections during the first few weeks of an animal’s life.

Final results

In the course of this project we have had to create new techniques by which we could comprehensively analyze our data. A significant part of this proposal aimed at looking into the numbers and distribution of a variety of inhibitory cell types in different brain areas across developmental time points. We therefore went into great length to develop Artificial Intelligence (AI)-based approaches for being able to detect neurons in mouse brain images of different histological samples that range from classical tissue sectioning and staining to Cleared Brains in an automatic manner. Furthermore, he also went further and also tackled the big problem of brain registration. Through the implementation of AI-based methods, he managed to segment and call a variety of brain regions of interest in both mouse and human brain imaging samples, obviating the need for a reference atlas.