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Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice
Journal article   Peer reviewed

Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice

Dake Huang, Fillan S Grady, Lila Peltekian and Joel C Geerling
Journal of comparative neurology (1911), Vol.529(4), pp.657-693
03/2021
DOI: 10.1002/cne.24975
PMCID: PMC7775907
PMID: 32621762

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Abstract

The parabrachial nucleus (PB) is a complex structure located at the junction of the midbrain and hindbrain. Its neurons have diverse genetic profiles and influence a variety of homeostatic functions. While its cytoarchitecture and overall efferent projections are known, we lack comprehensive information on the projection patterns of specific neuronal subtypes in the PB. In this study, we compared the projection patterns of glutamatergic neurons here with a subpopulation expressing the transcription factor Foxp2 and a further subpopulation expressing the neuropeptide Pdyn. To do this, we injected an AAV into the PB region to deliver a Cre‐dependent anterograde tracer (synaptophysin‐mCherry) in three different strains of Cre‐driver mice. We then analyzed 147 neuroanatomical regions for labeled boutons in every brain (n = 11). Overall, glutamatergic neurons in the PB region project to a wide variety of sites in the cerebral cortex, basal forebrain, bed nucleus of the stria terminalis, amygdala, diencephalon, and brainstem. Foxp2 and Pdyn subpopulations project heavily to the hypothalamus, but not to the cortex, basal forebrain, or amygdala. Among the few differences between Foxp2 and Pdyn cases was a notable lack of Pdyn projections to the ventromedial hypothalamic nucleus. Our results indicate that genetic identity determines connectivity (and therefore, function), providing a framework for mapping all PB output projections based on the genetic identity of its neurons. Using genetic markers to systematically classify PB neurons and their efferent projections will enhance the translation of research findings from experimental animals to humans. The parabrachial nucleus surrounds the superior cerebellar peduncle at the midbrain‐hindbrain junction. Its glutamatergic neurons form subpopulations with distinct genetic identities, two of which express Foxp2 and Pdyn. Here, we detail the location of Foxp2‐ and Pdyn‐expressing neurons within the larger Vglut2‐expressing population. We then use Cre‐conditional expression of synaptophysin‐mCherry to map the efferent projections of each population. Salient findings include the identification of glutamatergic output from the parabrachial nucleus to the rostral entorhinal cortex and lateral superior colliculus, plus an absence of Foxp2 or Pdyn output to the cerebral cortex, basal forebrain, and amygdala.
 dynorphin superior colliculus parabrachial complex Vglut2 rostromedial tegmental nucleus entorhinal cortex amygdalopiriform Slc17a6

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