Spontaneous Neural Network Oscillations in Hippocampus, Cortex, and Locus Coeruleus of Newborn Rat and Piglet Brain Slices

Rises of cytosolic Ca²⁺ (Ca_i ) associated with early network oscillations (ENOs) are important for brain maturation. Thus, developing neural networks are often studied by combining Ca_i imaging with electrophysiological recording of extracellular activity and/or intracellular “patch-clamp” analysis. At birth, some nervous systems such as medullary respiratory networks are functional while cortical circuits are yet quite immature. Here, we summarize our experimental approaches to investigate how both mature and developing neuron-glia networks in newborns generate spontaneous synchronized bursting and how such activity is modulated by (pharmacological) experimental manipulation mimicking neurological diseases or their treatment. For this, we studied ENOs in cortex and hippocampus of newborn rat and piglet brain slices, whereas ENO-like bursting in locus coeruleus was only analyzed in rat slices. All these activities are stable for several hours in superfusate of close-to-physiological ion content. Similar to isolated inspiratory network bursting, ENOs depend on a “Ca²⁺ /K⁺ antagonism” meaning that depressed bursting in elevated superfusate Ca²⁺ is countered by raised K⁺ . As further example for our findings, anoxia abolishes ENOs and bursting in locus coeruleus , whereas μ-opioid receptor activation blocks bursting, transforms burst pattern, or has no clear effect in locus coeruleus , hippocampus, and cortex, respectively. Multiphoton Ca_i imaging reveals different responses to neuromodulators in neurons versus neighboring astrocytic glia which forms the basis for their further discrimination via morphological fluorescence imaging of sulforhodamine-101 or glial acidic fibrillary protein. Our findings indicate that “electrophysiological imaging” in brain slices from neonatal mammals is a potent tool for studying spontaneously active (developing) central neuron-glia networks.