Author:

Keywords:

autonomic development, enteric nervous system, cholinergic neurons, ChA, development of projections, Science & Technology, Life Sciences & Biomedicine, Neurosciences, Zoology, Neurosciences & Neurology, CREST-DERIVED CELLS, ENTERIC NERVOUS-SYSTEM, INHIBITORY NEUROMUSCULAR-TRANSMISSION, NITRIC-OXIDE SYNTHASE, SYNAPTIC-TRANSMISSION, LONGITUDINAL MUSCLE, LARGE-INTESTINE, FETAL MICE, GUT, DIFFERENTIATION, ChAT, Animals, Animals, Newborn, Bacterial Proteins, Choline O-Acetyltransferase, Cholinergic Neurons, ELAV Proteins, Embryo, Mammalian, Enteric Nervous System, Gene Expression Regulation, Developmental, Luminescent Proteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myenteric Plexus, Nerve Tissue Proteins, Nitric Oxide Synthase Type I, beta-Galactosidase, 0608 Zoology, 1109 Neurosciences, 1116 Medical Physiology, Neurology & Neurosurgery, 3109 Zoology, 3209 Neurosciences

Abstract:

Cholinergic neurons are the major excitatory neurons of the enteric nervous system (ENS), and include intrinsic sensory neurons, interneurons, and excitatory motor neurons. Cholinergic neurons have been detected in the embryonic ENS; however, the development of these neurons has been difficult to study as they are difficult to detect prior to birth using conventional immunohistochemistry. In this study we used ChAT-Cre;R26R-YFP mice to examine the development of cholinergic neurons in the gut of embryonic and postnatal mice. Cholinergic (YFP+) neurons were first detected at embryonic day (E)11.5, and the proportion of cholinergic neurons gradually increased during pre- and postnatal development. At birth, myenteric cholinergic neurons comprised less than half of their adult proportions in the small intestine (25% of myenteric neurons were YFP+ at P0 compared to 62% in adults). The earliest cholinergic neurons appear to mainly project anally. Projections into the presumptive circular muscle were first observed at E14.5. A subpopulation of cholinergic neurons coexpress calbindin through embryonic and postnatal development, but only a small proportion coexpressed neuronal nitric oxide synthase. Our study shows that cholinergic neurons in the ENS develop over a protracted period of time.