Neuropaediatric and neuroarchaeology: understanding development to correct brain disorders

Abstract

The construction of the brain, with its 1015 synapses, follows a tight genetic programme. But at the same time, the neurons and networks follow a developmental sequence, from immature activities to adult ones. In essence, all voltage-gated and synapse-driven currents differ in young and adult neurons, and primitive networks generate patterns that have little to do with those that are relevant to adult behaviour. It is also clear that activity modulates the construction of functional units and neuronal ensembles, raising the fundamental question of the relationships and interactions between the genetic programme and activity. It has been suggested 1 that genes and activity have a checkpoint type of relationship, the latter confirming the validity of the former. In addition, there can be numerous errors in the formation of neuronal entities, and these are associated with severe neurological sequels. This raises the highly relevant clinical issue of the fate of neuronal ensembles that do not perform as they should do and end up misplaced and/or misconnected. How do these aberrant networks mature and how do they generate disorders? How do misplaced and/or misconnected neurons behave and malfunction to the extent that they exert adverse effects on the operation of the cortex? It has, for example, been suggested that these neurons remain 'frozen' in an immature state 1, 2, paving the way for interesting therapeutic advances. Of course, many other therapeutic advances have been sugg…