Development and plasticity of callosally projecting neurons. A model of complex wiring
CNB-CSIC. Madrid. Spain
In the mammalian brain, an ulterior exchange of information occurs through the corpus callosum (CC), which enables bilateral communication between hemispheres and the higher-order functions of our brain. CC alterations and altered patterns of interhemispheric activity accompany neurodevelopmental disorders such as CC agenesis (AgCC), autism spectrum disorders (ASD), schizophrenia, visual cortical impairments, and epilepsy. In my talk, I will discuss our studies on the specification of callosal neurons and the intrinsic plasticity associated with the process. Predominant views state that callosal and non-callosal fates are already predetermined when precursors generate the postmitotic neurons of the cortex: specific populations are born pre-programmed as callosal projecting neurons, while others, such as cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel, invariably project only ipsilaterally. Using a novel axonal-tracing strategy and GFP-targeted visualization of young neurons, we instead demonstrate the opposite, that callosal fates are discarded rather than acquired in L2/3 and 4 neurons (De León Reyes et la., Nat Commun 10, 4549 (2019)). Virtually all these neurons develop transient interhemispheric axons, and local-projecting fates emerge only as a postnatal alternative when exuberant callosal axons are gradually refined in an area- and layer-specific manner under the influence of sensory-specific inputs. This developmental exuberance during CC formation appears to be a strategy that enables plasticity and robust stereotyped wiring of the complex circuits added to mammals during evolution (de León Reyes et al. Development. 2020 Sep 28;147(18):dev189738; Bragg-Gonzalo L., Semin Cell Dev Biol. 2021 Oct;118:24-34). Furthermore, I will show that inhibitory interneurons select callosal wiring and diversify area-specific circuits through their control of CC refinement. This model of gradual restriction and elimination of potential connectivity through inhibition serves to explain the assembly of complex networks starting from a relatively restrictive variety of neuronal types.
Invited by Jean-Bernard Manent
Monday January 29th at 11 am – Inmed conference room