Hypocretin1/OrexinA axon targeting of laterodorsal tegmental nucleus neurons projecting to the rat medial prefrontal cortex. 2011

Esther del Cid-Pellitero, and Miguel Garzón
Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain.

Cortical activation and goal-directed behaviors characterize wakefulness. One cortical region especially involved in these phenomena is the medial prefrontal cortex (mPFC), which receives many inputs from cholinergic-containing neurons in brain stem structures implicated in arousal and wakefulness, such as the laterodorsal tegmental nucleus (LDT). Hypocretins/orexins (Hcrt/Ox), whose dysfunction is linked to narcolepsy, maintains arousal and stabilizes sleep-wakefulness states. We aim to determine if Hcrt1/OxA axons (1) innervate LDT neurons projecting to the mPFC, a target that would allow them to sustain arousal and wakefulness, and (2) target preferentially cholinergic versus noncholinergic LDT neurons. The retrograde tracer Fluorogold (FG) was injected in the rat mPFC, and dual immunolabeling of anti-FG and either anti-choline acetyltransferase (ChAT) or anti-Hcrt1/OxA antisera was determined in LDT. Also, actual Hcrt1/OxA targeting of cholinergic LDT neurons was ascertained by dual anti-Hcrt1/OxA and anti-ChAT detection in additional noninjected animals. Many LDT FG-labeled neurons were cholinergic (52.05 ± 3.72%). Hcrt1/OxA immunoprecipitate was observed in cytoplasm and granular vesicles within axons. Some Hcrt1/OxA-containing axons established asymmetric excitatory-type synapses with either unlabeled (46/438) or FG-labeled (7/438) dendrites. One-third of the target neurons were ChAT labeled. Hcrt1/OxA excitatory input to LDT neurons projecting to mPFC probably contributes to the wakefulness-enhancing actions of Hcrt/Ox impaired in narcoleptics.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D009434 Neural Pathways Neural tracts connecting one part of the nervous system with another. Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009479 Neuropeptides Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. Neuropeptide
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D000068797 Orexins Neuropeptide hormones that play a role in regulating a variety of behavioral and physiological processes in response to motivational stimuli. Hypocretin,Orexin,Hypocretin-1,Hypocretin-2,Hypocretins,Orexin-A,Orexin-B,Hypocretin 1,Hypocretin 2,Orexin A,Orexin B
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D014851 Wakefulness A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. Wakefulnesses

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