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FoxP2 brainstem neurons project to sodium appetite regulatory sites
Journal article   Peer reviewed

FoxP2 brainstem neurons project to sodium appetite regulatory sites

Jung-Won Shin, Joel C Geerling, Matthew K Stein, Rebecca L Miller and Arthur D Loewy
Journal of chemical neuroanatomy, Vol.42(1), pp.1-23
09/2011
DOI: 10.1016/j.jchemneu.2011.05.003
PMCID: PMC3148274
PMID: 21605659

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Abstract

► The transcription factor FoxP2 is found in salt-sensitive brainstem neurons. ► These neurons are localized in the pre-locus coeruleus and parabrachial nucleus. ► Their outputs target the basal forebrain, extended amygdala, and diencephalon. ► The densest projection was to the hypothalamus. ► These data provide a neuroanatomical framework for studying salt appetite. The transcription factor Forkhead box protein 2 (FoxP2) is expressed in two cell groups of the brainstem that have been implicated in sodium appetite regulation: the pre-locus coeruleus (pre-LC) and parabrachial nucleus – external lateral-inner subdivision (PBel-inner). Because the connections of these two groups are unknown, neuroanatomical tracing methods were used to define their central projections. The pre-LC outputs were first analyzed using an anterograde axonal tracer –Phaseolus vulgaris leucoagglutinin (PHAL) to construct a brain map. Next, we examined whether the FoxP2 immunoreactive (FoxP2+) neurons of the pre-LC contribute to these projections using a retrograde neuronal tracer – cholera toxin β-subunit (CTb). CTb was injected into selected brain regions identified in the anterograde tracing study. One week later the rats were killed, and brainstem sections were processed by a double immunohistochemical procedure to determine whether the FoxP2+ neurons in the pre-LC and/or PBel-inner contained CTb. FoxP2+ pre-LC neurons project to: (1) ventral pallidum; (2) substantia innominata and bed nucleus of the stria terminalis; (3) paraventricular, central medial, parafascicular, and subparafascicular parvicellular thalamic nuclei; (4) paraventricular (PVH), lateral, perifornical, dorsomedial (DMH), and parasubthalamic hypothalamic nuclei; and (5) ventral tegmental area (VTA), periaqueductal gray matter (PAG), dorsal and central linear raphe nuclei. FoxP2+ PBel-inner neurons project to the PVH and DMH, with weaker connections to the LHA, VTA, and PAG. Both the pre-LC and PBel-inner project to central sites implicated in sodium appetite, and related issues, including foraging behavior, hedonic responses to salt intake, sodium balance, and cardiovascular regulation, are discussed.
Parabrachial nucleus Ventral pallidum Bed nucleus of stria terminalis Thalamus Hypothalamus Pre-locus coeruleus Ventral tegmental area

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