title: Substance P and enkephalinergic synapses onto neurokinin-1 receptor-immunoreactive neurons in the pre-Bötzinger complex of rats.
abstract: Our previous studies have demonstrated that neurokinin-1 receptor (NK1R)-immunoreactive (ir) neurons in the pre-Bötzinger Complex (pre-BötC), the hypothesized kernel of respiratory rhythmogenesis, receive both glutamatergic excitatory and GABAergic or glycinergic inhibitory inputs. Neuromodulators, such as substance P (SP) and opioids, play important roles in normal respiratory activity and respiratory disorders. The identification of the relationship between neurotransmitters and NK1R-ir neurons at the cellular level is essential for understanding the synaptic interaction within the pre-BötC network. Using immunofluorescence and immunogold-silver staining, we wished to exploit SP and enkephalin (ENK) immunoreactivity and their relationships with glutamate, GABA, glycine, or NK1R in the pre-BötC in adult Sprague-Dawley rats. The pre-BötC contained a substantial amount of SP-ir and ENK-ir boutons. They were largely colocalized with glutamate and much less so with GABA. Glycine immunoreactivity was rarely found in either SP-ir or ENK-ir boutons. A number of SP-ir boutons were ENK-ir as well. Synapses were commonly found between SP-ir or ENK-ir terminals and NK1R-ir neurons in the pre-BötC. Most of them were asymmetric. Symmetric synapses made up 10% of all synapses examined between SP-ir boutons and NK1R-ir neurons, and 19% of ENK/NK1R synapses. Colocalization of SP and/or ENK with glutamate in boutons in the pre-BötC implies the combined synaptic release of excitatory amino acid and neuropeptides, which may exert combined post-synaptic effects onto NK1R-ir neurons and contribute to respiratory activity.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 17 Chang Le Xi Road, Xi'an 710032, PR, 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: Xiao-Yan
authors.initials: XY
authors.lastname: Wei
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Liu
authors.forename: Fumino
authors.initials: F
authors.lastname: Fujiyama
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
mesh_terms: D000818:Animals; D004745:Enkephalins / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis*; D012125:Respiratory Center / Q000378:metabolism / Q000648:ultrastructure*; D012143:Respiratory Physiological Phenomena; D013373:Substance P / Q000096:biosynthesis*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D004745:Enkephalins; D018040:Receptors, Neurokinin-1; D013373:Substance P; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine