Selective Mesoaccumbal Pathway Inactivation Affects Motivation but Not Reinforcement-Based Learning in Macaques

Vancraeyenest, Pascaline; Arsenault, John; Li, Xiaolian; Zhu, Qi; Kobayashi, Kenta; Isa, Kaoru; Isa, Tadashi; Vanduffel, Wim

doi:10.1016/j.neuron.2020.07.013

Cited by 34 publications

(26 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After the injection sites relative to the grid were decided, the monkey was anesthetized again and the AAV vectors were injected into the intended location: the VTA. The injection needles were prepared as previously described ( Vancraeyenest et al. 2020 ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Divergent Whole Brain Projections from the Ventral Midbrain in Macaques

et al. 2021

Self Cite

View full text Add to dashboard Cite

To understand the connectome of the axonal arborizations of dopaminergic midbrain neurons, we investigated the anterograde spread of highly sensitive viral tracers injected into the ventral tegmental area (VTA) and adjacent areas in 3 macaques. In 2 monkeys, injections were centered on the lateral VTA with some spread into the substantia nigra, while in one animal the injection targeted the medial VTA with partial spread into the ventro-medial thalamus. Double-labeling with antibodies against transduced fluorescent proteins (FPs) and tyrosine hydroxylase indicated that substantial portions of transduced midbrain neurons were dopaminergic. Interestingly, cortical terminals were found either homogeneously in molecular layer I, or more heterogeneously, sometimes forming patches, in the deeper laminae II–VI. In the animals with injections in lateral VTA, terminals were most dense in somatomotor cortex and the striatum. In contrast, when the medial VTA was transduced, dense terminals were found in dorsal prefrontal and temporal cortices, while projections to striatum were sparse. In all monkeys, orbitofrontal and occipito-parietal cortex received strong and weak innervation, respectively. Thus, the dopaminergic ventral midbrain sends heterogeneous projections throughout the brain. Furthermore, our results suggest the existence of subgroups in meso-dopaminergic neurons depending on their location in the primate ventral midbrain.

show abstract

Section: Methodsmentioning

confidence: 99%

“…2006 ), motor behavior ( Kunori et al. 2014 ), attention ( Noudoost and Moore 2011 ) and motivation and effort ( Walton and Bouret 2019 ; Vancraeyenest et al. 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Divergent Whole Brain Projections from the Ventral Midbrain in Macaques

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent advances in specific neuronal manipulation tools have drastically enhanced our understandings of the functional roles of individual neural pathways in small animals such as rodents (24,53). Nonetheless, the application of pathway-selective manipulations to non-human primates is still largely limited by using either optogenetic terminal activation (19)(20)(21) or double-vector methods (15)(16)(17)(18), neither of which is capable of testing dissociable function of multiple neural pathways in individual subjects. Using a chemogenetic approach, the current study succeeded in the double-dissociation of the roles of two distinct pathways in individual monkeys.…”

Section: R a F Tmentioning

confidence: 99%

“…Several studies have so far shown behavioral modification with reversible pathway-selective dissection in monkeys, where a double-viral vector infection method was used to manipulate the activity of a single neuronal pathway (15)(16)(17)(18). This approach, however, is not suitable for investigating multiple neural pathways independently within a single animal.…”

Section: Introductionmentioning

confidence: 99%

Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

Oyama

Hori

Nagai

et al. 2021

Preprint

View full text Add to dashboard Cite

The primate prefrontal cortex (PFC) is situated at the core of higher brain functions by linking and cooperating with the caudate nucleus (CD) and mediodorsal thalamus (MD) via neural circuits. However, the distinctive roles of these prefronto-subcortical pathways remain elusive. Combining in vivo neuronal projection mapping with chemogenetic synaptic silencing, we reversibly dissected key pathways from PFC to the CD and MD individually in single monkeys. We found that silencing the bilateral PFC-MD projections, but not the PFC-CD projections, impaired performance in a spatial working memory task. Conversely, silencing the unilateral PFC-CD projection, but not the PFC-MD projection, altered preference in a free-choice task. These results revealed dissociable roles of the prefronto-subcortical pathways in working memory and decision-making, representing the technical advantage of imaging-guided pathway-selective chemogenetic manipulation for dissecting neural circuits underlying cognitive functions in primates.

show abstract

“…In another recent study, the technique was used in combination with functional imaging in monkeys performing cognitive tasks (Vancraeyenest et al, 2020). Specifically, the authors reversibly inactivated the connections originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) in monkeys.…”

Section: Directional and Pathway-selective Approachesmentioning

confidence: 99%

Combining Brain Perturbation and Neuroimaging in Non-human Primates

Klink¹,

jean-francois.aubry@espci.fr²,

Ferrera³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesions. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state-of-the-art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods.

show abstract

Selective Mesoaccumbal Pathway Inactivation Affects Motivation but Not Reinforcement-Based Learning in Macaques

Cited by 34 publications

References 69 publications

Divergent Whole Brain Projections from the Ventral Midbrain in Macaques

Divergent Whole Brain Projections from the Ventral Midbrain in Macaques

Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

Combining Brain Perturbation and Neuroimaging in Non-human Primates

Contact Info

Product

Resources

About