Presynaptic inhibition of pre‐Bötzinger complex neurons in high calcium and disturbed seizure‐like inspiratory bursting in low calcium in newborn rat brainstem slices

Abstract

Inspiratory pre‐Bötzinger complex (preBötC) rhythm in brainstem slices in physiological (3mM) K+ is depressed by raising superfusate Ca2+ from 1mM to 1.5mM. Here, we studied cellular mechanisms of such Ca2+ block of preBötC rhythm and quantified extracellular preBötC interneuron and preBötC‐driven hypoglossal (XII) motoneuron responses to varied Ca2+ and Mg2+. In 400µm thick newborn rat brainstem slices, preBötC/XII rhythm stopped after <2h in 3K+‐1.2Ca2+, but was restored in 7mM K+. Stable preBötC/XII rhythm in 7K+‐1.2Ca2+ was blocked by 2‐3mM Ca2+ without effect on resting potential or input resistance of preBötC and non‐preBötC inspiratory neurons or tonic neurons. preBötC/XII burst rates increased while amplitudes decreased in <1.2Ca2+ until rhythms stopped in <0.25Ca2+. =0.8mM Ca2+evoked seizure‐like activity, partially masking inspiratory XII bursts. Lowering Mg2+ from 1mM to 0.25mM in 7K+‐1.2Ca2+ did not affect preBötC/XII rhythms, whereas 3mM Mg2+ depressed their rate and amplitude to 43% and 82% of control, respectively. Findings show that inspiratory interneuron and XII motoneuron networks in brainstem slices are relatively insensitive to extracellular Mg2+, but generate stable rhythm only in 0.8‐1.2mM Ca2+. Lack of postsynaptic membrane effects suggests that Ca2+ block of isolated preBötC networks involves primarily presynaptic mechanisms. Supported by CIHR‐MFN, CIHR, AHFMR.