The developing brainstem generates periodic spontaneous neural activity (SNA). SNA is thought to be crucial for the maturation of motor neurons and associated neural networks. Beginning around embryonic day five (E5), SNA is driven by cholinergic nicotinic neurotransmission (NT) with only minor modulatory inputs from ƴ‐aminobutyric acid GABA/glycinergic NT. Here we tested the effects of embryonic nicotine exposure on the neurogenesis of SNA in brainstem regions that later support homeostatic functions such as breathing. We hypothesized that brain stem motor circuits will compensate for nicotine blockade of nicotine acetylcholine receptors (nAChR) to maintain SNA by rapidly shifting to GABA/glycinergic NT. To test our hypothesis we used electrical physiological recordings and pharmacology before and after chronic nicotine exposure to probe for nicotine evoked plasticity of brain stem derived SNA in chick embryos on E5‐E5.5. Results show that nicotine abolished SNA at millimolar concentrations similar to those detected in human plasma following a single cigarette. However SNA recovered quickly (蠄 4 h) while still in the presence of nicotine suggesting that compensatory neurotransmitter(s) was driving SNA activity. Indeed, results show that GABA/glycinergic NT is required to drive SNA in the absence of nAChR availability demonstrating a form of activity dependent neural plasticity. In summary, our results show that the developing brain stem can rapidly adapt to perturbations of previously well‐defined CNS neurotransmitters to maintain SNA, and suggests that neurotransmitter phenotypic plasticity is a critical feature of the embryonic brainstem that may function to maintain the integrity of homeostatic oscillatory network functions in vivo.

Brain‐related breathing problems are common in early life. Despite intensive investigations into mammalian breathing control, our understanding of respiratory rhythm generation is still unclear, especially during the prenatal period. We aim to develop the avian embryo as a more tractable prenatal model to study breathing related behaviors. Birds are highly active endotherms, like mammals, and provide access for manipulations that mammals cannot. In the rodent, automatic breathing behaviors have been identified in isolated transverse brainstem slices. We hypothesize that there is a similar complex within the avian brainstem. Thus, our goal is to identify the central pattern generator for breathing in the bird. We used an activity dependent dye, electrical recordings, and Nissl staining to generate a neuroanatomical brain stem map. We examined isolated brain stems from Corturnix japonica near internal pipping when breathing movements are present. Results suggest that birds possess a spontaneously generated rhythm in the ventral lateral medulla similar to mammals. We further show that in some preparations tonic activity became rhythmic when inhibitory neurotransmission was blocked. These results suggest critical differences between the prenatal development of central breathing control of bird and mammals, including the importance of GABA and glycine neurotransmission prior to parturition.