A discrete dopaminergic projection from the incertohypothalamic A13 cell group to the dorsolateral periaqueductal gray in rat

Fany Messanvi, Ellie Eggens-Meijer, Benno Roozendaal, Johannes J. van der Want*

*Corresponding author for this work

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    Abstract

    Several findings have indicated an involvement of dopamine in panic and defensive behaviors. The dorsolateral column of the periaqueductalgray (dlPAG) is crucially involved in the expression of panic attacks in humans and defensive behaviors, also referred to as panic like behaviors, in animals. Although the dlPAG is known to receive a specific innervation of dopaminergic fibers and abundantly expresses dopamine receptors, the origin of this dopaminergic input is largely unknown. This study aimed at mapping the dopaminergic projections to the dlPAG in order to provide further insight into the panic-like related behavior circuitry of the dlPAG. For this purpose, the retrograde tracer cholera toxin subunitb (CTb) was injected into the dlPAG of male Wistar rats and double immunofluorescence for CTb and tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine, was performed. Neurons labeled for both CTb and TH were counted in different dopaminergic cell groups. The findings indicate that the dopaminergic nerve terminals present in the dlPAG originate from multiple dopamine-containing cell groups in the hypothalamus and mesencephalon. Interestingly, the A13 cell group is the main source of dopaminergic afferents to the dlPAG and contains at least 45% of the total number of CTb/TH-positive neurons. Anterograde tracing with biotinylated dextran amine (BDA) combined with double immunofluorescence for BD and TH confirmed the projections from the A13 cell group to the dlPAG. The remainder of the dopamine-positive terminals present in the dlPAG was found to originate from the extended A10 cell group and the A11 group. The A13 cell group is known to send dopaminergic efferents to several other brain regions implicated in defensive behavior, including the central amygdala and ventromedial hypothalamus. Therefore, although direct behavioral evidence is lacking, our finding that the A13 cell group is also themain source of dopaminergic input to the dlPAG suggests that dopamine might contribute to the regulation of dlPAG mediated defensive behaviors.

    Original languageEnglish
    Article number41
    Number of pages14
    JournalFrontiers in neuroanatomy
    Volume7
    DOIs
    Publication statusPublished - 6-Dec-2013

    Keywords

    • dorsolateral periaqueductal gray (dlPAG)
    • dopamine
    • incertohypothalamic A11
    • and A13 cell groups
    • defensive behavior
    • panic
    • AFFECTIVE DEFENSE BEHAVIOR
    • MELANIN-CONCENTRATING HORMONE
    • POSTERIOR HYPOTHALAMIC AREA
    • SOCIAL-EMOTIONAL REACTIVITY
    • VENTRAL TEGMENTAL AREA
    • MEDIAL PREOPTIC AREA
    • ZONA INCERTA
    • BRAIN-STEM
    • ANTERIOR HYPOTHALAMUS
    • AFFERENT CONNECTIONS

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