Periodic Reporting for period 4 - InterWiring (Wiring up the SomatoSensory Cortex)
Reporting period: 2021-05-01 to 2022-04-30
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 process them changes extremely with age, in order to perhaps extract more refined information 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 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 to regulate sensory processing.
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 major alterations over after-birth development. Overall our findings identify a novel window of developmental structural and functional rearrangements in the mouse cortex that defines its engagement in higher order brain computations. Further, utilizing molecular approaches we have identified key proteins for the proper developmental integration of inhibitory cells into their circuit during the first few postnatal weeks.
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 automatically and comprehensively detect neurons in mouse brain images of different histological samples that range from classical histological samples to whole brains that had been made transparent. Furthermore, we also aimed to expland these tools to tackle the big problem of brain registration against standard atlases, an approach that is routinely used in brain surgery. Through the implementation of AI-based methods, we managed to segment and categorize a variety of brain regions of interest in both mouse and human brain imaging samples, obviating the need for a reference atlas.