Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system

Babiczky, Ákos [Babiczky, Ákos (Neurobiológia, ps...), author] Neural Network and Behavior; Matyas, Ferenc ✉ [Mátyás, Ferenc (Neurobiológia), author] Department of Anatomy and Histology (ÁTE / ATI); Institute of Experimental Medicine; Neural Network and Behavior

English Article (Journal Article) Scientific
Published: ELIFE 2050-084X 2050-084X 11 Paper: e78813 2022
  • SJR Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous): D1
Identifiers
Fundings:
  • National Research, Development and Innovation Fund(FK124434)
  • National Research, Development and Innovation Fund(K138836)
  • National Research, Development and Innovation Fund(KKP126998)
  • New National Excellence Program of the Ministry for Innovation and Technology(ÚNKP-21-5-ÁTE-2)
  • New National Excellence Program of the Ministry for Innovation and Technology(ÚNKP-18-3-II-BME-55)
  • New National Excellence Program of the Ministry for Innovation and Technology(ÚNKP-20-3-II-BME-24)
  • New National Excellence Program of the Ministry for Innovation and Technology(ÚNKP-21-3-II-BME-61)
Subjects:
  • Neurology
Prefrontal cortical influence over the mesolimbic system – including the nucleus accumbens (NAc) and the ventral tegmental area (VTA) – is implicated in various cognitive processes and behavioral malfunctions. The functional versatility of this system could be explained by an underlying anatomical complexity; however, the detailed characterization of the medial prefrontal cortical (mPFC) innervation of the NAc and VTA is still lacking. Therefore, combining classical retrograde and conditional viral tracing techniques with multiple fluorescent immunohistochemistry, we sought to deliver a precise, cell- and layer-specific anatomical description of the cortico-mesolimbic pathways in mice. We demonstrated that NAc- (mPFC NAc ) and VTA-projecting mPFC (mPFC VTA ) populations show different laminar distribution (layers 2/3–5a and 5b–6, respectively) and express different molecular markers. Specifically, calbindin and Ntsr1 are specific to mPFC NAc neurons, while mPFC VTA neurons express high levels of Ctip2 and FoxP2, indicating that these populations are mostly separated at the cellular level. We directly tested this with double retrograde tracing and Canine adenovirus type 2 -mediated viral labeling and found that there is indeed minimal overlap between the two populations. Furthermore, whole-brain analysis revealed that the projection pattern of these populations is also different throughout the brain. Taken together, we demonstrated that the NAc and the VTA are innervated by two, mostly nonoverlapping mPFC populations with different laminar distribution and molecular profile. These results can contribute to the advancement in our understanding of mesocorticolimbic functions and its disorders in future studies.
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2024-05-30 00:07