title: GABAergic and glycinergic synapses onto neurokinin-1 receptor-immunoreactive neurons in the pre-Bötzinger complex of rats: light and electron microscopic studies.
abstract: The pre-Bötzinger complex (preBötC) in the ventrolateral medulla is thought to be the kernel for respiratory rhythm generation. Neurons in the preBötC contain intense neurokinin-1 receptor (NK1R) immunoreactivity. Some of these neurons in the adult preBötC are presumed to be the pre-inspiratory interneurons that are essential for generating respiratory rhythm in the neonate. Chloride-mediated synaptic inhibition is critical for rhythmogenesis in the adult. The present study used immunofluorescence histochemistry and immunogold-silver staining to determine the inhibitory synaptic relationship between glutamic acid decarboxylase (GAD)- or glycine transporter 2 (GlyT2)-immunoreactive (ir) boutons and NK1R-ir neurons in the preBötC of adult rats. Under the confocal microscope, we found that GAD- and GlyT2-ir boutons were in close apposition to NK1R-ir somas and dendrites in the preBötC. Under the electron microscope, GAD- and GlyT2-ir terminals were in close apposition to NK1R-ir somas and dendrites. Symmetric synapses were identified between GAD- or GlyT2-ir terminals and NK1R-ir neurons. A total of 51.6% GAD-ir and 38.2% GlyT2-ir terminals were found to contact or make synapses with NK1R-ir profiles, respectively. GAD- and GlyT2-ir terminals synapsed not only upon NK1R-ir neurons but also upon NK1R immuno-negative neurons. NK1R-ir neurons received both symmetric (presumed inhibitory) and asymmetric (presumed excitatory) synapses. Thus, the present findings provide the morphological basis for inhibitory inputs to NK1R-ir neurons in the preBötC, consistent with the suggestion that chloride-mediated synaptic inhibition may contribute importantly to rhythm generation by controlling the membrane potential trajectory and resetting rhythmic bursting of the kernel neurons in the adult.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Margaret T T
authors.initials: MT
authors.lastname: Wong-Riley
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Liu
authors.forename: Xi-Ying
authors.initials: XY
authors.lastname: Jiao
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D000818:Animals; D048429:Cell Size / Q000502:physiology; D018118:Chloride Channels / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins; D007150:Immunohistochemistry; D008526:Medulla Oblongata / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009433:Neural Inhibition / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism* / Q000648:ultrastructure; D012125:Respiratory Center / Q000378:metabolism* / Q000648:ultrastructure; D012143:Respiratory Physiological Phenomena; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D018118:Chloride Channels; D050487:Glycine Plasma Membrane Transport Proteins; D018040:Receptors, Neurokinin-1; C493269:Slc6a5 protein, rat; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D005998:Glycine