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Pre‐locus coeruleus and parabrachial neurons projecting to the ventral tegmental area are innervated by serotonergic neurons: a potential pathway for the salt appetite hedonic system

Salt appetite is a behavioral state where sodium deficient animals seek and ingest substances that contain salt. The consumption of salt results in a pleasureful experience that undoubtedly uses a reward pathway of the brain. One of these areas is the ventral tegmental area (VTA) which is associated with many appetitive behaviors, but it is undetermined if it contributes salt appetite. The purpose of this study is to determine whether there is a serotonin (5HT) → pre‐locus coeruleus (pre‐LC) and lateral parabrachial nucleus (PB) → VTA pathway. Neurons in the pre‐LC and the external lateral PB express c‐Fos after dietary sodium deprivation for longer than a week, and these two groups of neurons also constitutively express the transcription factor Forkhead box protein 2 (FoxP2). Retrograde tracing studies with cholera toxin β subunit (CTb) confirmed that pre‐LC and PBel project to the VTA. Approximately 40% and 30% of the FoxP2 cells were co‐labeled with CTb in the pre‐LC and PBel, respectively. Over 50% of the neurons that were FoxP2 and CTb co‐labeled were innervated by 5HT neurons in both the pre‐LC and PBel. Retrograde tracing showed that 5HT neurons that project to the pre‐LC have their cell bodies in the dorsal raphe (DR), median raphe, and medial longitudinal fasciculus (mlf); and for PBel the 5HT cell bodies were in the DR, mlf, and area postrema. Supported by NHLBI NIH Grant #HL‐25449 and NINDS NIH Grant#NS057105