Abstract
Anatomical and functional evidence suggests that the PFC is fairly unique among all cortical regions, as it not only receives input from, but also robustly projects back to mesopontine monoaminergic and cholinergic cell groups. Thus, the PFC is in position to exert a powerful top-down control over several state-setting modulatory transmitter systems that are critically involved in the domains of arousal, motivation, reward/aversion, working memory, mood regulation, and stress processing. Regarding this scenario, the origin of cortical afferents to the ventral tegmental area (VTA), laterodorsal tegmental nucleus (LDTg), and median raphe nucleus (MnR) was here compared in rats, using the retrograde tracer cholera toxin subunit b (CTb). CTb injections into VTA, LDTg, or MnR produced retrograde labeling in the cortical mantle, which was mostly confined to frontal polar, medial, orbital, and lateral PFC subdivisions, along with anterior- and mid-cingulate areas. Remarkably, in all of the three groups, retrograde labeling was densest in layer V pyramidal neurons of the infralimbic, prelimbic, medial/ventral orbital and frontal polar cortex. Moreover, a lambda-shaped region around the apex of the rostral pole of the nucleus accumbens stood out as heavily labeled, mainly after injections into the lateral VTA and LDTg. In general, retrograde PFC labeling was strongest following injections into MnR and weakest following injections into VTA. Altogether, our findings reveal a fairly similar set of prefrontal afferents to VTA, LDTg, and MnR, further supporting an eminent functional role of the PFC as a controller of major state-setting mesopontine modulatory transmitter systems.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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N/A.
Abbreviations
- Aca:
-
Anterior commissure, anterior part
- Acb:
-
Accumbens nucleus
- AcbRP:
-
Accumbens nucleus, rostral pole
- AcbSh:
-
Accumbens nucleus, shell
- AId1:
-
Dorsal agranular insular cortex, dorsal part
- AId2:
-
Dorsal agranular insular cortex, ventral part
- AIp:
-
Posterior agranular insular cortex
- AIv:
-
Ventral agranular insular cortex
- Cc:
-
Corpus callosum
- cg:
-
Cingulum
- Cg1:
-
Cingulate cortex, area 1
- Cg2:
-
Cingulate cortex, area 2
- Cl:
-
Claustrum
- CLi:
-
Caudal linear nucleus of the raphe
- CPu:
-
Caudate putamen
- CTb:
-
Cholera toxin subunit b
- Den:
-
Dorsal endopiriform nucleus
- DI:
-
Dysgranular insular cortex
- DLO1:
-
Dorso-lateral orbital cortex, dorsal part
- DLO2:
-
Dorso-lateral orbital cortex, ventral part
- DP:
-
Dorsal peduncular cortex
- DR:
-
Dorsal raphe nucleus
- DRC:
-
Dorsal raphe nucleus, caudal part
- DRD:
-
Dorsal raphe nucleus, dorsal part
- DRI:
-
Dorsal raphe nucleus, interstitial part
- DRL:
-
Dorsal raphe nucleus, lateral part
- DRV:
-
Dorsal raphe nucleus, ventral part
- DTgP:
-
Dorsal tegmental nucleus, pericentral part
- DTT:
-
Dorsal tenia tecta
- EOV:
-
Ependym of the olfactory ventricle
- Fmi:
-
Forceps minor of the corpus callosum
- FP:
-
Frontal polar cortex
- FPl:
-
Frontal polar cortex, lateral part
- FPm:
-
Frontal polar cortex, medial part
- GI:
-
Granular insula cortex
- IF:
-
Interfascicular nucleus
- IL:
-
Infralimbic cortex
- IP:
-
Interpeduncular nucleus
- Λ:
-
Area lambda
- LDTg:
-
Laterodorsal tegmental nucleus
- LO:
-
Lateral orbital cortex
- LHb:
-
Lateral habenula
- lPFC:
-
Lateral prefrontal cortex
- mPFC:
-
Medial prefrontal cortex
- M1:
-
Primary motor cortex
- M2:
-
Secondary motor cortex
- MnR:
-
Median raphe nucleus
- MO:
-
Medial orbital cortex
- NeuN:
-
Neuronal nuclear protein
- oPFC:
-
Orbital prefrontal cortex
- PHA-L:
-
Phaseolus vulgaris-Leucoagglutinin
- PBP:
-
Parabrachial pigmented nucleus of the VTA
- PFC:
-
Prefrontal cortex
- PMnR:
-
Paramedian raphe nucleus
- PN:
-
Paranigral nucleus of the VTA
- PrL:
-
Prelimbic cortex
- RLi:
-
Rostral linear nucleus of the raphe
- S1:
-
Primary somatosensory cortex
- SNC:
-
Substantia nigra, pars compacta
- SNR:
-
Substantia nigra, reticular part
- SMI-32:
-
Neurofilament H marker SMI-32
- VGLUT2:
-
Vesicular glutamate transporter type 2
- VGLUT3:
-
Vesicular glutamate transporter type 3
- VLO:
-
Ventrolateral orbital cortex
- VLOp:
-
Ventrolateral orbital cortex, posterior part
- VO:
-
Ventral orbital cortex
- VTA:
-
Ventral tegmental area
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The authors thank Ana M.P. Campos for expert technical assistance and Mario Costa Cruz for help with confocal microscopy procedures.
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Preparation of this manuscript was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo –FAPESP: Grant numbers 2017/16473–6 (M.M.) and 2020/01318–8 (J.D.J.).
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Souza, R., Bueno, D., Lima, L.B. et al. Top-down projections of the prefrontal cortex to the ventral tegmental area, laterodorsal tegmental nucleus, and median raphe nucleus. Brain Struct Funct 227, 2465–2487 (2022). https://doi.org/10.1007/s00429-022-02538-2
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DOI: https://doi.org/10.1007/s00429-022-02538-2