Single-neuron projectome of mouse prefrontal cortex

Le, Gao; Sang, Liu; Gou, Lingfeng; Hu, Yachuang; Liu, Yanhe; Deng, Li; Ma, Danyi; Wang, Haifang; Yang, Qiaoqiao; Chen, Zhaoqin; Liu, Dechen; Qiu, Shou; Wang, Xiaofei; Wang, Danying; Wang, Xinran; Ren, Biyu; Liu, Qingxu; Chen, Tianzhi; Shi, Xiaoxue; Yao, Haishan; Xu, Chun; Li, C.; Sun, Yan-Gang; Li, Anan; Luo, Qingming; Gong, Hui; Xu, Ning-long; Yan, Jun

doi:10.1038/s41593-022-01041-5

Cited by 107 publications

(100 citation statements)

References 58 publications

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“…Considering that mPFC innervates the VTA with a relatively sparse axon arborization ( Carr and Sesack, 2000 ; Geisler and Zahm, 2005 ), these result further support that these populations are rather nonoverlapping at the single-cell level. However, complete projection pattern analysis revealed that neurons of these populations collateralize extensively to innervate different areas throughout the brain, in accordance with the findings of Gao et al, 2022 . Specifically, mPFC NAc neurons showed IT-like projection pattern (mainly ipsi- and contralateral cortical, amygdalar, and striatal targets), while mPFC VTA efferents resembled PT neurons (mainly ipsilateral mesencephalic and diencephalic targets).…”

Section: Discussionsupporting

confidence: 85%

“…This suggests that either some PT-like mPFC neurons innervate the striatum or, alternatively, some IT-like neurons express Ctip2 in the mPFC. Previous results reported that PT neurons can innervate the striatum ( Economo et al, 2018 ; Matho et al, 2021 ; Gao et al, 2022 ) supporting the first option. However, to the best of our knowledge, there is no direct evidence for the complete absence of Ctip2 expression in IT neurons, so we cannot completely rule out the second possibility either.…”

Section: Discussionmentioning

confidence: 64%

“…A recent publication ( Gao et al, 2022 ) investigating fully reconstructed mPFC neurons demonstrated that IT and PT neurons collateralize extensively, although this collateralization was strongest for traditional target regions of IT and PT classes. This notion is further supported by similar experiments carried out in the M1 cortex ( Callaway, 2021 ; Muñoz-Castañeda et al, 2021 ; Peng et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Several well-established classification systems exist, based on anatomical, physiological, molecular, and connectivity profile of excitatory cortical neurons ( Harris et al, 2014 ; Harris et al, 2019 ; Harris and Shepherd, 2015 ; Baker et al, 2018 ; Bakken et al, 2021 ; Gao et al, 2022 ). A widely accepted one divides principal neurons to three major classes according to their laminar distribution and projection pattern.…”

Section: Introductionmentioning

confidence: 99%

“…However, some studies suggest that this classification might be oversimplified and not universally applicable to all cortical areas ( Groh et al, 2010 ; Kim et al, 2015 ). Indeed, a recent publication ( Gao et al, 2022 ) divided prefrontal cortical neurons into even more new subtypes based on their genetic identity and connectivity. These results implicate that experiments involving cortical projection neurons embedded in the mesocorticolimbic system require a combination of cell-, layer-, and class-selective approaches to ensure appropriate precision.…”

Section: Introductionmentioning

confidence: 99%

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

Babiczky

Mátyás

2022

eLife

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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- (mPFCNAc) and VTA-projecting mPFC (mPFCVTA) 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 mPFCNAc neurons, while mPFCVTA 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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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Babiczky

Mátyás

2022

eLife

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Mapping the Function of Whole‐Brain Projection at the Single Neuron Level

Zhou

et al. 2022

Advanced Science

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Axonal projection conveys neural information. The divergent and diverse projections of individual neurons imply the complexity of information flow. It is necessary to investigate the relationship between the projection and functional information at the single neuron level for understanding the rules of neural circuit assembly, but a gap remains due to a lack of methods to map the function to whole‐brain projection. Here an approach is developed to bridge two‐photon calcium imaging in vivo with high‐resolution whole‐brain imaging based on sparse labeling with the genetically encoded calcium indicator GCaMP6. Reliable whole‐brain projections are captured by the high‐definition fluorescent micro‐optical sectioning tomography (HD‐fMOST). A cross‐modality cell matching is performed and the functional annotation of whole‐brain projection at the single‐neuron level (FAWPS) is obtained. Applying it to the layer 2/3 (L2/3) neurons in mouse visual cortex, the relationship is investigated between functional preferences and axonal projection features. The functional preference of projection motifs and the correlation between axonal length in MOs and neuronal orientation selectivity, suggest that projection motif‐defined neurons form a functionally specific information flow, and the projection strength in specific targets relates to the information clarity. This pipeline provides a new way to understand the principle of neuronal information transmission.

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Organization of orbitofrontal‐auditory pathways in the Mongolian gerbil

Ying

Hamlette

Nikoobakht

et al. 2023

J of Comparative Neurology

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Sound perception is highly malleable, rapidly adjusting to the acoustic environment and behavioral demands. This flexibility is the result of ongoing changes in auditory cortical activity driven by fluctuations in attention, arousal, or prior expectations. Recent work suggests that the orbitofrontal cortex (OFC) may mediate some of these rapid changes, but the anatomical connections between the OFC and the auditory system are not well characterized. Here, we used virally mediated fluorescent tracers to map the projection from OFC to the auditory midbrain, thalamus, and cortex in a classic animal model for auditory research, the Mongolian gerbil (Meriones unguiculatus). We observed no connectivity between the OFC and the auditory midbrain, and an extremely sparse connection between the dorsolateral OFC and higher order auditory thalamic regions. In contrast, we observed a robust connection between the ventral and medial subdivisions of the OFC and the auditory cortex, with a clear bias for secondary auditory cortical regions. OFC axon terminals were found in all auditory cortical lamina but were significantly more concentrated in the infragranular layers. Tissue‐clearing and lightsheet microscopy further revealed that auditory cortical‐projecting OFC neurons send extensive axon collaterals throughout the brain, targeting both sensory and non‐sensory regions involved in learning, decision‐making, and memory. These findings provide a more detailed map of orbitofrontal‐auditory connections and shed light on the possible role of the OFC in supporting auditory cognition.

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Single-neuron projectome of mouse prefrontal cortex

Cited by 107 publications

References 58 publications

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

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

Mapping the Function of Whole‐Brain Projection at the Single Neuron Level

Organization of orbitofrontal‐auditory pathways in the Mongolian gerbil

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