Quantifying Dopaminergic Innervation in Rodents Using Unbiased Stereology

Reynolds, Lauren M.; Pantoja-Urbán, Andrea Harée; MacGowan, Del; Manitt, Colleen; Nouel, Dominique; Flores, Cecilia

doi:10.1007/978-1-0716-2799-0_2

Cited by 2 publications

(2 citation statements)

References 41 publications

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“…It would therefore be impossible to accurately quantify the number of axons. Using unbiased stereology to quantify varicosities is a valid, well-characterized and straightforward alternative (Reynolds et al, 2022). We agree that it would be very interesting to see how UNC5c mRNA and protein levels change over time in summer and winter hamsters, both in males, as the reviewer suggests here, and in females.…”

Section: Referencesmentioning

confidence: 62%

“…Unbiased stereology is the gold-standard technique for estimating populations of anatomical objects, such as axons, that are so numerous that it would be impractical or impossible to measure every single one. Here and elsewhere we generally provide results as densities and areas of occupancy (Reynolds et al, 2022). To avoid confusion, we now clarify that we are counting the width of the area that dopamine axons occupy (rather than the dopamine axon "bundle").…”

Section: Referencesmentioning

confidence: 99%

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The scheduling of adolescence with Netrin-1 and UNC5C

Hoops

Kyne

Salameh

et al. 2024

eLife

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Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

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Section: Referencesmentioning

confidence: 62%

Section: Referencesmentioning

confidence: 99%

The scheduling of adolescence with Netrin-1 and UNC5C

Hoops

Kyne

Salameh

et al. 2024

eLife

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Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice

et al. 2023

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Initiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to sex and exact timing of use. The cellular and molecular underpinnings explaining this differential sensitivity to detrimental drug effects remain unexplained. The Netrin-1/DCC guidance cue system segregates cortical and limbic dopamine pathways in adolescence. Here we show that amphetamine, by dysregulating Netrin-1/DCC signaling, triggers ectopic growth of mesolimbic dopamine axons to the prefrontal cortex, only in early-adolescent male mice, underlying a male-specific vulnerability to enduring cognitive deficits. In adolescent females, compensatory changes in Netrin-1 protect against the deleterious consequences of amphetamine on dopamine connectivity and cognitive outcomes. Netrin-1/DCC signaling functions as a molecular switch which can be differentially regulated by the same drug experience as function of an individual’s sex and adolescent age, and lead to divergent long-term outcomes associated with vulnerable or resilient phenotypes.

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Quantifying Dopaminergic Innervation in Rodents Using Unbiased Stereology

Cited by 2 publications

References 41 publications

The scheduling of adolescence with Netrin-1 and UNC5C

The scheduling of adolescence with Netrin-1 and UNC5C

Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice

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