Present address: Instituto de Neurociencias de Alicante CSIC, Universidad Miguel 13 Hernández 03550 Alicante, Spain.
Timing of developmental sequences in different brain structures: physiological and pathological implications
Article first published online: 19 JUN 2012
Published 2012. This article is a U.S. Government work and is in the public domain in the USA
European Journal of Neuroscience
Special Issue: EARLY BRAIN REPAIR AND PROTECTION
Volume 35, Issue 12, pages 1846–1856, June 2012
How to Cite
Dehorter, N., Vinay, L., Hammond, C. and Ben-Ari, Y. (2012), Timing of developmental sequences in different brain structures: physiological and pathological implications. European Journal of Neuroscience, 35: 1846–1856. doi: 10.1111/j.1460-9568.2012.08152.x
- Issue published online: 19 JUN 2012
- Article first published online: 19 JUN 2012
- Received 17 February 2012, revised 4 April 2012, accepted 9 April 2012
- developmental sequences;
The developing brain is not a small adult brain. Voltage- and transmitter-gated currents, like network-driven patterns, follow a developmental sequence. Studies initially performed in cortical structures and subsequently in subcortical structures have unravelled a developmental sequence of events in which intrinsic voltage-gated calcium currents are followed by nonsynaptic calcium plateaux and synapse-driven giant depolarising potentials, orchestrated by depolarizing actions of GABA and long-lasting NMDA receptor-mediated currents. The function of these early patterns is to enable heterogeneous neurons to fire and wire together rather than to code specific modalities. However, at some stage, behaviourally relevant activities must replace these immature patterns, implying the presence of programmed stop signals. Here, we show that the developing striatum follows a developmental sequence in which immature patterns are silenced precisely when the pup starts locomotion. This is mediated by a loss of the long-lasting NMDA-NR2C/D receptor-mediated current and the expression of a voltage-gated K+ current. At the same time, the descending inputs to the spinal cord become fully functional, accompanying a GABA/glycine polarity shift and ending the expression of developmental patterns. Therefore, although the timetable of development differs in different brain structures, the g sequence is quite similar, relying first on nonsynaptic events and then on synaptic oscillations that entrain large neuronal populations. In keeping with the ‘neuroarcheology’ theory, genetic mutations or environmental insults that perturb these developmental sequences constitute early signatures of developmental disorders. Birth dating developmental disorders thus provides important indicators of the event that triggers the pathological cascade leading ultimately to disease.