Early NMDA receptor-driven waves of activity in the developing neocortex: physiological or pathological network oscillations?

Abstract

Several patterns of coherent activity have been described in developing cortical structures, thus providing a general framework for network maturation. A detailed timely description of network patterns at circuit and cell levels is essential for the understanding of pathogenic processes occurring during brain development. Disturbances in the expression timetable of this pattern sequence are very likely to affect network maturation. This review focuses on the maturation of coherent activity patterns in developing neocortical structures. It emphasizes the intrinsic and synaptic cellular properties that are unique to the immature neocortex and, in particular, the critical role played by extracellular glutamate in controlling network excitability and triggering synchronous network waves of activity.

Rosa Cossart is currently leading a research group in the Institut de Neurobiologie de la Méditerranée (INSERM U901, Marseille, France). Her research interests focus on the maturation of functional cortical GABAergic microcircuits. She was not initially trained as a neurobiologist but as a physicist with a strong education in mathematics, studying engineering in the Ecole Centrale de Paris. In 2001, she obtained a PhD in biophysics at Paris VI University under the supervision of Dr C. Bernard in the laboratory directed by Dr Yehezkel Ben-Ari. She next pursued her research training as a postdoctoral fellow in Professor Rafael Yuste's laboratory at Columbia University (New York, USA). There she developed a novel approach to study network dynamics in brain slices that combines two-photon calcium imaging with online mathematical analysis and targeted electrophysiological recordings. Since 2002 she has been as a permanent research fellow in the Centre National de la Recherche Scientifique. She received in 2005 a ‘Medaille de Bronze’ from the CNRS, an award that recognizes her early research achievements.

Figure 1. Spontaneous activity patterns in the developing rodent cortex

NC: neocortex; CC: cerebellar cortex; H: hippocampus.

Figure 2. A general sequence for the maturation of coherent electrical activity patterns

Schematic representation of the sequential maturation of synchronized electrical activity patterns from late embryonic stages to the end of the first postnatal week in neocortical rodent slices (Allene et al. 2008). At embryonic stages electrical activity is uncorrelated. At birth it becomes synchronized through gap junctions and is supported by the activation of voltage-gated intrinsic conductances (SPAs). Later, network patterns are synapse-driven by glutamatergic (ENOs) or GABAergic (GDPs) transmission. Note that extrasynaptic glutamate receptors are also likely to be involved in the generation of ENOs. With the exception of ENOs, the same sequence was found in the developing hippocampus (Crépel et al. 2007).

Figure 3. ENOs present striking similarities with both a physiological and a pathological network pattern

A, ENO-associated membrane potential depolarisations recorded in current clamp mode before (a) and after (b) decreasing the rate of the perfusion from 4 to 1 ml min⁻¹ (data taken from Allene et al. 2008). Similar effects were found in anoxic/aglycaemic perfusion conditions (see Allene et al. 2008). B, comparison between the membrane potential depolarization (top black trace), the calcium fluorescence signal (green) and the spontaneous excitatory postsynaptic currents (sEPSCs, bottom black, V_m=−60 mV) associated with the spontaneous ENO illustrated in (Aa) and with a stage III retinal wave (reprinted from Blankenship et al. (2009) with permission from Elsevier). Note the similarity between the two patterns. C, same as in B but comparing ENOs produced by a mild anoxic condition occurring when decreasing the perfusion rate (Ab) with slow network oscillations (SNOs) induced by pharmacological EEAT blockade with DL-TBOA (unpublished data from L. Aniksztejn & A.A. Cattani).