title: Neural connection supporting endogenous 5-hydroxytryptamine influence on autonomic activity in medial prefrontal cortex.
abstract: 5-hydroxytryptamine (5-HT) transmission in the medial prefrontal cortex (mPFC) enhances or suppresses signal outflow to influence emotion-/cognition-based function performances and, putatively, the autonomic responses. The top-down cortical modulation of autonomic activities may be mediated in part through projections from mPFC to brain stem dorsal vagal complex (DVC). The abundant and heterogeneous densities of 5-HT fibers across laminae in mPFC suggest serotonergic innervation of mPFC-DVC projection neurons whereby endogenous 5-HT acts to regulate autonomic activities. The present study investigated the physical relationship between 5-HT fibers and the autonomic-related mPFC neurons by examining and quantitatively characterizing the 5-HT contacts upon retrogradely labeled mPFC-DVC projection neurons in pre- and infra-limbic cortices (PrL/IL) with light and electron microscopies combined with immunocytochemistry for 5-HT and presynaptic vesicle marker synaptophysin (Syn). 5-HT varicosities were observed, under confocal microscope, to form close appositions to or, at ultrastructural level, to form asymmetric axodendritic synapses and direct contacts upon the target neurons. About 16% of the entire 5-HTergic varicosities in lamina V of PrL/IL coexpressed Syn and about 24% of the peri-somatic 5-HTergic swellings demonstrated Syn-immunoreactivity (ir), suggesting a low frequency of putative synapses estimated at optical level. Ultrastructurally, examination of thirty-seven serially cut thin 5-HT boutons closely apposed to the labeled dendritic profiles demonstrated that only three contacts presented with identifiable asymmetric, synaptic membrane specializations. These data provide the first and direct morphological evidence supporting that endogenous 5-HT may be released mainly via direct contacts bearing no identifiable synaptic specializations as well as synapses, targeting autonomic-related mPFC neurons for autonomic regulation.
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China; Department of Orthopedics, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Hao-Qiang
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China; Department of Dermatology, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jin-Lian
authors.initials: JL
authors.lastname: Li
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Ya-Cheng
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China; Department of Anatomy, Histology and Embryology, Basic Medical College, Fujian Medical University, Fuzhou, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yu
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Ying-Shing
authors.initials: YS
authors.lastname: Chan
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China. Electronic address: zfxmq@126.com.
authors.forename: Fu-Xing
authors.initials: FX
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China. Electronic address: deptanat@fmmu.edu.cn.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000818:Animals; D017776:Autonomic Pathways / Q000166:cytology / Q000378:metabolism*; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016708:Synaptophysin; D012701:Serotonin
keywords: 5-hydroxytryptamine; Autonomic control; Dorsal vagal complex; Medial prefrontal cortex; Rat; Tract tracing