A road map to the beauty of the brain – how to build a brain -- Rodney Douglas, ETH-Zürich

Giacomo inaugurated the 2018 CapoCaccia meeting by saying a few words about the organisation of the workshop and introducing us to the key contributors who helped organise the meeting this year - Moritz Milde and Gaby Michel, and others like Elisa Donati and Nicoletta Risi. 

The first lecture 'A road map to the beauty of the brain' was delivered by Rodney Douglas. 

Rodney began his lecture by reminding us of a 3000-year old problem – how the ‘silent’ single cell (in the form of an ‘egg’) turns into a functional chicken, i.e., how the blank slate (tabula rasa) of developing cortical circuits accommodates emergence of functional specialisation contributing to animal behaviour!

Rodney began by describing how in developing vertebrates, embryonic precursors form neural tube (progenitor of CNS – brain and the spinal cord). Along the antero-posterior axis (2D-grid), fore-, mid- and hind-brain structures are laid together with spinal cord by morphogenic gradients (notch, delta, sonic hedgehog etc). Rodney argues – how is this architecture algorithmically stable that in future will give rise to the final structure of computation?

Rolling up of a 2D sheet leads to the organisation of sensory, integrative and motor areas along the dorso-ventral axes – where cortex and basal ganglia serves both sensory + motor function. The head end of the neural tube folds ventrally at the cervical flexure and mesencephalic flexure and then expands into primary brain vesicles. Abhi asks if cross-transplantations expts have been performed to confirm identities of this spatial organisation. Rodney says genetic fate-mapping studies specifically addressed this for many decades.

 After laying out the general organisation, Rodney focused on the generation of cellular diversity – cortical neurons are generated in a limited period of development, varying from days to months depending on the species. Two main progenitor populations in the dorsal telencephalon are responsible for the generation of cortical excitatory projection neurons (with a cell body and a great length of axon): (a) ventricular zone (VZ) progenitors or radial glia cells (RGC); and (b) subventricular zone (SVZ) or intermediate progenitors. Inhibitory interneurons are born in medial and lateral ganglionic eminences (MGE and LGE) – migrate north to integrate into cortical layers. Ach neurons are born in MGE. It is still unclear what facilitates or restricts these processes and the extent to which there exist sensitive windows during their generation that are disrupted in brain disorders.  We took a coffee break at this point to come back and further discuss how these details construct a functional circuit.