VTA-projecting cerebellar neurons mediate stress-dependent depression-like behavior

Baek, Soo Ji; Park, Jinsung; Kim, Jinhyun; Yamamoto, Yukio; Tanaka-Yamamoto, Keiko

doi:10.1101/2021.08.25.457606

Cited by 2 publications

(7 citation statements)

References 116 publications

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“…Activity changes in these studies denote that the cerebellum has functional effects on the recorded brain regions through direct or indirect network connections. The direct functional connections have been verified by recording synaptic transmission from the neurons in target brain regions ex vivo , upon the photostimulation of channelrhodopsin-expressing DCN neuronal terminals ( Gornati et al, 2018 ; Xiao et al, 2018 ; Carta et al, 2019 ; Vaaga et al, 2020 ; Baek et al, 2021 ).…”

Section: Techniques To Unravel the Complexity Of Cerebellar Efferent Pathwaysmentioning

confidence: 95%

“…Thus, even though anatomical connections from the DCN to the VTA appear to be minor, the VTA receives direct inputs from the DCN. It was originally suggested that projections originate from the FN and DN ( Parker et al, 2014 ), yet a study in preprint at this moment showed using adeno-associated virus (AAV)-based circuit mapping that the DCN-VTA connections were contralateral, and originated mainly from the DN and partly from the IPN ( Baek et al, 2021 ). The study also showed that among all the VTA regions, the dorsolateral posterior VTA was the main target of the DCN projections.…”

Section: New Lines Of Evidence On Efferent Pathways Associated With Non-motor Functions: Direct Pathwaysmentioning

confidence: 99%

“…Using optogenetic manipulation of axons of DCN neurons in the VTA, activation of this pathway was demonstrated to be rewarding and to be required for social behaviors ( Carta et al, 2019 ). On the other hand, it was demonstrated in the abovementioned preprint study using chemogenetic manipulation of VTA-projecting DCN neurons that chronic activation of these neurons triggers depression-like behaviors ( Baek et al, 2021 ). Although it is still unknown as to how the activation of the DCN efferent pathways projecting to the VTA can positively and negatively affect mental conditions, i.e., rewarding and depression, this may be reasonable given the heterogeneous functions of the VTA ( Morales and Margolis, 2017 ).…”

Section: New Lines Of Evidence On Efferent Pathways Associated With Non-motor Functions: Direct Pathwaysmentioning

confidence: 99%

“…The second is the pathway from the DCN to the mediodorsal and ventrolateral thalamic nuclei, via which glutamate neurons control dopamine release by regulating presynaptic terminals in the mPFC. As DCN neurons directly project to the VTA ( Snider et al, 1976 ; Parker et al, 2014 ; Beier et al, 2015 ; Carta et al, 2019 ; Baek et al, 2021 ), this direct projection may in turn regulate dopamine release in the mPFC. All pathways shown or suggested to date may mediate cerebellar-mPFC circuits ( Figure 1C ), and regulation through these various pathways appears to be reasonable, considering the functions of the mPFC, which require broad types of inputs.…”

Section: New Lines Of Evidence On Efferent Pathways Associated With Non-motor Functions: Indirect Pathwaysmentioning

confidence: 99%

“…Indeed, network property analyses in a cell type-specific manner were performed by injecting AAV with a Cre-dependent cassette into the DCN of cell type-specific Cre transgenic mice ( Lefler et al, 2014 ; Ankri et al, 2015 ; Prekop et al, 2018 ; Zhou M. et al, 2020 ). Some studies also used viral vectors demonstrating retrograde transport, such as AAVs engineered to have efficient retrograde access [rAAV2-retro, ( Tervo et al, 2016 )] or a canine adenoviral vector [CAV2 ( Del Rio et al, 2019 )], to label projection-specific DCN neurons ( Hashimoto et al, 2018 ; Frontera et al, 2020 ; Sathyamurthy et al, 2020 ; Baek et al, 2021 ). To observe disynaptic connections from the DCN, anterograde transsynaptic tracing was also performed ( Xiao et al, 2018 ; Bohne et al, 2019 ; Kelly et al, 2020 ) by injecting recombinase-expressing AAV serotype 1 with transsynaptic properties ( Zingg et al, 2017 ) or AAV expressing Cre fused with wheat germ agglutinin (WGA) ( Gradinaru et al, 2010 ) into the DCN ( Xiao et al, 2018 ; Bohne et al, 2019 ; Kelly et al, 2020 ).…”

Section: Techniques To Unravel the Complexity Of Cerebellar Efferent Pathwaysmentioning

confidence: 99%

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Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

et al. 2021

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The cerebellum has a long history in terms of research on its network structures and motor functions, yet our understanding of them has further advanced in recent years owing to technical developments, such as viral tracers, optogenetic and chemogenetic manipulation, and single cell gene expression analyses. Specifically, it is now widely accepted that the cerebellum is also involved in non-motor functions, such as cognitive and psychological functions, mainly from studies that have clarified neuronal pathways from the cerebellum to other brain regions that are relevant to these functions. The techniques to manipulate specific neuronal pathways were effectively utilized to demonstrate the involvement of the cerebellum and its pathways in specific brain functions, without altering motor activity. In particular, the cerebellar efferent pathways that have recently gained attention are not only monosynaptic connections to other brain regions, including the periaqueductal gray and ventral tegmental area, but also polysynaptic connections to other brain regions, including the non-primary motor cortex and hippocampus. Besides these efferent pathways associated with non-motor functions, recent studies using sophisticated experimental techniques further characterized the historically studied efferent pathways that are primarily associated with motor functions. Nevertheless, to our knowledge, there are no articles that comprehensively describe various cerebellar efferent pathways, although there are many interesting review articles focusing on specific functions or pathways. Here, we summarize the recent findings on neuronal networks projecting from the cerebellum to several brain regions. We also introduce various techniques that have enabled us to advance our understanding of the cerebellar efferent pathways, and further discuss possible directions for future research regarding these efferent pathways and their functions.

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Section: Techniques To Unravel the Complexity Of Cerebellar Efferent Pathwaysmentioning

confidence: 95%

Section: New Lines Of Evidence On Efferent Pathways Associated With Non-motor Functions: Direct Pathwaysmentioning

confidence: 99%

Section: New Lines Of Evidence On Efferent Pathways Associated With Non-motor Functions: Direct Pathwaysmentioning

confidence: 99%

Section: New Lines Of Evidence On Efferent Pathways Associated With Non-motor Functions: Indirect Pathwaysmentioning

confidence: 99%

Section: Techniques To Unravel the Complexity Of Cerebellar Efferent Pathwaysmentioning

confidence: 99%

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Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

et al. 2021

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A Systematic Review of Direct Outputs from the Cerebellum to the Brainstem and Diencephalon in Mammals

2022

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The cerebellum is involved in many motor, autonomic and cognitive functions, and new tasks that have a cerebellar contribution are discovered on a regular basis. Simultaneously, our insight into the functional compartmentalization of the cerebellum has markedly improved. Additionally, studies on cerebellar output pathways have seen a renaissance due to the development of viral tracing techniques. To create an overview of the current state of our understanding of cerebellar efferents, we undertook a systematic review of all studies on monosynaptic projections from the cerebellum to the brainstem and the diencephalon in mammals. This revealed that important projections from the cerebellum, to the motor nuclei, cerebral cortex, and basal ganglia, are predominantly di- or polysynaptic, rather than monosynaptic. Strikingly, most target areas receive cerebellar input from all three cerebellar nuclei, showing a convergence of cerebellar information at the output level. Overall, there appeared to be a large level of agreement between studies on different species as well as on the use of different types of neural tracers, making the emerging picture of the cerebellar output areas a solid one. Finally, we discuss how this cerebellar output network is affected by a range of diseases and syndromes, with also non-cerebellar diseases having impact on cerebellar output areas.

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VTA-projecting cerebellar neurons mediate stress-dependent depression-like behavior

Cited by 2 publications

References 116 publications

Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

A Systematic Review of Direct Outputs from the Cerebellum to the Brainstem and Diencephalon in Mammals

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