We report a signaling mechanism in rats between mother and fetus aimed at preparing fetal neurons for delivery. In immature neurons, γ-aminobutyric acid (GABA) is the primary excitatory neurotransmitter. We found that, shortly before delivery, there is a transient reduction in the intracellular chloride concentration and an excitatory-to-inhibitory switch of GABA actions. These events were triggered by oxytocin, an essential maternal hormone for labor. In vivo administration of an oxytocin receptor antagonist before delivery prevented the switch of GABA actions in fetal neurons and aggravated the severity of anoxic episodes. Thus, maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery.

Thalamic gamma rhythms help develop highly spatially and laminar-specific ascending cortical projections.

Early in development, cortical networks generate particular patterns of activity that participate in cortical development. The dominant pattern of electrical activity in the neonatal rat neocortex in vivo is a spatially confined spindle-burst. Here, we studied network mechanisms of generation of spindle-bursts in the barrel cortex of neonatal rats using a superfused cortex preparation in vivo. Both spontaneous and sensory-evoked spindle-bursts were present in the superfused barrel cortex. Pharmacological analysis revealed that spindle-bursts are driven by glutamatergic synapses with a major contribution of AMPA/kainate receptors, but slight participation of NMDA receptors and gap junctions. Although GABAergic synapses contributed minimally to the pacing the rhythm of spindle-burst oscillations, surround GABAergic inhibition appeared to be crucial for their compartmentalization. We propose that local spindle-burst oscillations, driven by glutamatergic synapses and spatially confined by GABAergic synapses, contribute to the development of barrel cortex during the critical period of developmental plasticity.

GABA depolarizes immature cortical neurons. However, whether GABA excites immature neocortical neurons and drives network oscillations as in other brain structures remains controversial. Excitatory actions of GABA depend on three fundamental parameters: the resting membrane potential ( E_m), reversal potential of GABA ( E_GABA), and threshold of action potential generation ( V_thr). We have shown recently that conventional invasive recording techniques provide an erroneous estimation of these parameters in immature neurons. In this study, we used noninvasive single N-methyl-d-aspartate and GABA channel recordings in rodent brain slices to measure both E_mand E_GABAin the same neuron. We show that GABA strongly depolarizes pyramidal neurons and interneurons in both deep and superficial layers of the immature neocortex (P2–P10). However, GABA generates action potentials in layer 5/6 (L5/6) but not L2/3 pyramidal cells, since L5/6 pyramidal cells have more depolarized resting potentials and more hyperpolarized V_thr. The excitatory GABA transiently drives oscillations generated by L5/6 pyramidal cells and interneurons during development (P5–P12). The NKCC1 co-transporter antagonist bumetanide strongly reduces [Cl⁻]_i,GABA-induced depolarization, and network oscillations, confirming the importance of GABA signaling. Thus a strong GABA excitatory drive coupled with high intrinsic excitability of L5/6 pyramidal neurons and interneurons provide a powerful mechanism of synapse-driven oscillatory activity in the rodent neocortex in vitro. In the companion paper, we show that the excitatory GABA drives layer-specific seizures in the immature neocortex.