Sequential Generation of Two Distinct Synapse-Driven Network Patterns in Developing Neocortex

Abstract

Developing cortical networks generate a variety of coherent activity patterns that participate in circuit refinement. Early network oscillations (ENOs) are the dominant network pattern in the rodent neocortex for a short period after birth. These large-scale calcium waves were shown to be largely driven by glutamatergic synapses albeit GABA is a major excitatory neurotransmitter in the cortex at such early stages, mediating synapse-driven giant depolarizing potentials (GDPs) in the hippocampus. Using functional multineuron calcium imaging together with single-cell and field potential recordings to clarify distinct network dynamics in rat cortical slices, we now report that the developing somatosensory cortex generates first ENOs then GDPs, both patterns coexisting for a restricted time period. These patterns markedly differ by their developmental profile, dynamics, and mechanisms: ENOs are generated before cortical GDPs (cGDPs) by the activation of glutamatergic synapses mostly through NMDARs; cENOs are low-frequency oscillations (ϳ0.01 Hz) displaying slow kinetics and gradually involving the entire network. At the end of the first postnatal week, GABA-driven cortical GDPs can be reliably monitored; cGDPs are recurrent oscillations (ϳ0.1 Hz) that repetitively synchronize localized neuronal assemblies. Contrary to cGDPs, cENOs were unexpectedly facilitated by short anoxic conditions suggesting a contribution of glutamate accumulation to their generation. In keeping with this, alterations of extracellular glutamate levels significantly affected cENOs, which are blocked by an enzymatic glutamate scavenger. Moreover, we show that a tonic glutamate current contributes to the neuronal membrane excitability when cENOs dominate network patterns. Therefore, cENOs and cGDPs are two separate aspects of neocortical network maturation that may be differentially engaged in physiological and pathological processes.

Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

“…These data suggest that the network oscillations in the superficial neocortical layers of mice during P5-6 are mainly cGDPs (24). cGDPs appear to be strongly dependent on the actions of GABA as they are almost completely blocked by the GABA A receptor antagonist (24). Our study indicates that, besides GABAergic transmission, CX26-mediated electrical coupling between excitatory neurons contributes to the expression of cGDPs at early postnatal stages.…”

“…We found that the network oscillations in the superficial neocortical layers of mice during P5-6 display two features: (i) the frequency is ∼0.1 Hz, and (ii) the synchronicity duration is less than 200 ms. These data suggest that the network oscillations in the superficial neocortical layers of mice during P5-6 are mainly cGDPs (24). cGDPs appear to be strongly dependent on the actions of GABA as they are almost completely blocked by the GABA A receptor antagonist (24).…”

“…Two distinct network oscillations, cortical early network oscillations (cENOs) and cortical giant depolarizing potentials (cGDPs), were observed in the developing rat cortex (24). The cENOs peak around birth (P0-3) and are no longer present when cGDPs dominate the network (P6-P8) (24), although there is a transition period (P4-5) during which both patterns can be simultaneously recorded in the rat neocortex (24).…”

“…2 A and B). Active cells are neurons exhibiting at least one calcium transient within the period of recording (24). We analyzed the proportion of active cells, which was defined as the percentage of active cells among all calcium dye-loaded cells in one field, and the frequency of spontaneous activity of active cells, which was defined as the number of calcium transients per second, as previously reported (25).…”

Artificial CSF Motion Ensures Rhythmic Activity in the Developing CNS Ex Vivo: A Mechanical Source of Rhythmogenesis?

“…Endogenous rhythmic activity is a key feature of immature neural networks that has been described in many developing structures of the CNS, including the retina, cochlea, spinal cord, hindbrain, cerebellum, thalamus, hippocampus, and cortex (Galli and Maffei, 1988;Ben-Ari et al, 1989;Yuste et al, 1992;O'Donovan, 1999;Garaschuk et al, 2000;Ben-Ari, 2002;Leinekugel et al, 2002;Yvert et al, 2004;Hunt et al, 2005;Dupont et al, 2006;Spitzer, 2006;Momose-Sato et al, 2007;Allène et al, 2008;Blankenship and Feller, 2010), and shown to be essential for the establishment of functional network connectivity (Penn et al, 1998;Hanson and Landmesser, 2004;Cang et al, 2005). Although previous studies have been devoted to deciphering the cellular and synaptic mechanisms underlying such activity (Tabak et al, 2000;Ben-Ari, 2002), the primal mechanism responsible for the generation of immature rhythms remains largely unknown.…”