Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking

Kim, Christina K.; Li, Ye; Jennings, Joshua H.; Pichamoorthy, Nandini; Tang, Daniel D.; Yoo, Ai-Chi Wang; Ramakrishnan, Charu; Deisseroth, Karl

doi:10.1016/j.cell.2017.07.020

Cited by 126 publications

(150 citation statements)

References 69 publications

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“…As an additional form of validation, we confirmed projection-specific expression of two of the top differentially expressed genes across treatments, Tnnc1 and Pou3f1, by comparing fluorescence in situ hybridization (FISH) with projection-specific labeling (Figure 1I). Further validating these findings, our RNA-seq results replicated the major hits reported in a recent microarray study (Kim et al 2017) that compared expression between PL-NAc and PL-VTA neurons (> 2.8-fold preferential enrichment for Nptx2 , Nrn1 , and Sccpdh in PL-NAc; and > 2.7-fold preferential enrichment for Bcl11b / CTIP2 , Chst8 , and Tcerg1l in PL-VTA; Table S1). …”

Section: Resultssupporting

confidence: 87%

Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex

Murugan

Jang

Park

et al. 2017

Cell

259

207

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Social behaviors are crucial to all mammals. Although the prelimbic cortex (PL, part of medial prefrontal cortex) has been implicated in social behavior, it is not clear which neurons are relevant, nor how they contribute. We found that PL contains anatomically and molecularly distinct subpopulations that target 3 downstream regions that have been implicated in social behavior: the nucleus accumbens (NAc), amygdala, and ventral tegmental area. Activation of NAc-projecting PL neurons (PL-NAc), but not the other subpopulations, decreased preference for a social target. To determine what information PL-NAc neurons convey, we recorded selectively from them, and found that individual neurons were active during social investigation, but only in specific spatial locations. Spatially-specific manipulation of these neurons bidirectionally regulated the formation of a social-spatial association. Thus, the unexpected combination of social and spatial information within the PL-NAc may contribute to social behavior by supporting social-spatial learning.

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Section: Resultssupporting

confidence: 87%

Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex

Murugan

Jang

Park

et al. 2017

Cell

259

207

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“…It is presently unknown whether any of the pathwaydefined afferents to the NAc have distinctive activity patterns at a population level, although the inputs are associated with distinct cognitive processes (Floresco, 2015;Humphries and Prescott, 2010). Neural activity has been recorded in forebrain regions upstream of the NAc during reward-seeking tasks, but there is variable activity among neurons in those areas as well (Ambroggi et al, 2008;Ciocchi et al, 2015;Do-Monte et al, 2017;Kim et al, 2017;Li et al, 2016;Otis et al, 2017;Tye et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Coordinated Reductions in Excitatory Input to the Nucleus Accumbens Underlie Food Consumption

Reed

Lafferty

Mendoza

et al. 2018

Neuron

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Reward-seeking behavior is regulated by a diverse collection of inputs to the nucleus accumbens (NAc). The information encoded in each excitatory afferent to the NAc is unknown, in part because it is unclear when these pathways are active in relation to behavior. Here we compare the activity profiles of amygdala, hippocampal, and thalamic inputs to the NAc shell in mice performing a cued reward-seeking task using GCaMP-based fiber photometry. We find that the rostral and caudal ends of the NAc shell are innervated by distinct but intermingled populations of forebrain neurons that exhibit divergent feeding-related activity. In the rostral NAc shell, a coordinated network-wide reduction in excitatory drive correlates with feeding, and reduced input from individual pathways is sufficient to promote it. Overall, the data suggest that pathway-specific input activity at a population level may vary more across the NAc than between pathways.

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“…TAM inducible CreER/LoxP system laid the foundations of significant discoveries in adult and embryonic neural stem cell fate mapping (Berg et al, 2019;Bond et al, 2015;Fuentealba et al, 2015;Gao et al, 2014), gene functions (Kuo et al, 2006), as well as neuronal subtypes and activity dependent neural circuitry (Kim et al, 2017;Paul et al, 2017;Ye et al, 2016). Is the potential side effect of TAM a vulnerable Achille's heel to cell lineage tracing and/or genetic targeting studies?…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptomic analysis revealed long-lasting adverse effects of prenatal tamoxifen administration on neurogenesis in prenatal and adult brains

C¹,

Zhou

Liu

et al. 2019

Preprint

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CreER/LoxP system has enabled precise gene manipulation in distinct cell subpopulations at any specific time point upon tamoxifen (TAM) administration. This system is widely accepted to track neural lineages and study gene functions. We have observed prenatal TAM treatment caused high rate of delayed delivery and mortality of pups. These substances could promote undesired results, leading to data misinterpretation. Here, we report that TAM administration during early stages of cortical neurogenesis promoted precocious neural differentiation, while inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, and cortical patterning in neonatal and postnatal offspring. Mechanistically, single cell RNA sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays showed TAM could exert these drastic effects mainly through dysregulating the expression of Dmrta2 and Wnt8b. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of prenatal tamoxifen administration on corticogenesis, suggesting that tamoxifen-induced CreER-LoxP system may not be suitable for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.

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Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking

Cited by 126 publications

References 69 publications

Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex

Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex

Coordinated Reductions in Excitatory Input to the Nucleus Accumbens Underlie Food Consumption

Single cell transcriptomic analysis revealed long-lasting adverse effects of prenatal tamoxifen administration on neurogenesis in prenatal and adult brains

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