Cerebellar Modulation of Mesolimbic Dopamine Transmission Is Functionally Asymmetrical

Holloway, Zade; Paige, Nick B.; Comstock, Josiah F.; Nolen, Hunter G.; Sable, Helen J.K.; Lester, Deranda B.

doi:10.1007/s12311-019-01074-w

Cited by 21 publications

(12 citation statements)

References 87 publications

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“…Here, we focused on the nucleus accumbens (NAc), a complex limbic structure that shares reward, motivation and affective functionality with the CB 51,52 . Stimulation of CB cortex or deep cerebellar nuclei (DCN) modulates levels of NAc dopamine --an important, but not exclusive, regulator of NAc functions [53][54][55][56][57][58][59] . However, how the CB connects to NAc is unknown.…”

Section: Introductionmentioning

confidence: 99%

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

D’Ambra

Jung

Ganesan

et al. 2020

Preprint

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Traditionally viewed as a motor control center, the cerebellum (CB) is now recognized as an integral part of a broad, long-range brain network that serves limbic functions and motivates behavior. This diverse CB functionality has been at least partly attributed to the multiplicity of its outputs. However, relatively little attention has been paid to CB connectivity with subcortical limbic structures, and nothing is known about how the CB connects to the nucleus accumbens (NAc), a complex striatal region with which the CB shares functionality in motivated behaviors. Here, we report findings from in vivo electrophysiological experiments that investigated the functional connectivity between CB and NAc. We found that electrical microstimulation of deep cerebellar nuclei (DCN) modulates NAc spiking activity. This modulation differed in terms of directionality (excitatory vs. inhibitory) and temporal characteristics, in a manner that depends on NAc subregions: in the medial shell of NAc (NAcMed), slow inhibitory responses prevailed over excitatory ones, whereas the proportion of fast excitatory responses was greater in the NAc core (NAcCore) compared to NAcMed. Slow inhibitory modulation of NAcCore was also observed but it required stronger CB inputs compared to NAcMed. Finally, we observed shorter onset latencies for excitatory responses in NAcCore than in NAcMed, which argues for differential connectivity. If different pathways provide signal to each subregion, the divergence likely occurs downstream of the CB because we did not find any response-type clustering within DCN. Because there are no direct monosynaptic connections between CB and NAc, we performed viral tracing experiments to chart disynaptic pathways that could potentially mediate the newly discovered CB-NAc communication. We identified two anatomical pathways that recruit the ventral tegmental area and intralaminar thalamus as nodes. These pathways and the functional connectivity they support could underlie CB’s role in motivated behaviors.

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Section: Introductionmentioning

confidence: 99%

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

D’Ambra

Jung

Ganesan

et al. 2020

Preprint

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“…Moreover, the electrical stimulation of the fastigial nucleus increased only the release of [ 3 H]-DA in the ipsilateral caudate nucleus (Nieoullon et al, 1978), and the electrical stimulation of the posterior interpositus nucleus increased the release of [ 3 H]-DA in ipsilateral SNpc and in the contralateral caudate nucleus while decreasing the release [ 3 H]-DA in the ipsilateral caudate nucleus (Nieoullon and Dusticier, 1980). In addition, the electrical stimulation of the mouse cerebellar dentate nucleus was elicited mainly in the contralateral nucleus accumbens (NAc), determining an asymmetrical and lateralized DA release (Figure 9; Holloway et al, 2019).…”

Section: Cerebellar-midbrain Dopaminergic Pathwaysmentioning

confidence: 98%

The Cerebellar Dopaminergic System

Flace

Livrea

Basile

et al. 2021

Front. Syst. Neurosci.

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In the central nervous system (CNS), dopamine (DA) is involved in motor and cognitive functions. Although the cerebellum is not been considered an elective dopaminergic region, studies attributed to it a critical role in dopamine deficit-related neurological and psychiatric disorders [e.g., Parkinson's disease (PD) and schizophrenia (SCZ)]. Data on the cerebellar dopaminergic neuronal system are still lacking. Nevertheless, biochemical studies detected in the mammalians cerebellum high dopamine levels, while chemical neuroanatomy studies revealed the presence of midbrain dopaminergic afferents to the cerebellum as well as wide distribution of the dopaminergic receptor subtypes (DRD1-DRD5). The present review summarizes the data on the cerebellar dopaminergic system including its involvement in associative and projective circuits. Furthermore, this study also briefly discusses the role of the cerebellar dopaminergic system in some neurologic and psychiatric disorders and suggests its potential involvement as a target in pharmacologic and non-pharmacologic treatments.

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“…Finally, electrophysiological, pharmacological and immunohistochemical research studies investigated how different neurotransmitter systems, such as noradrenergic, cholinergic or dopaminergic system, can modulate the synaptic transmission and thereby influence the functional output through activation of specific cerebellar receptor subtypes (156)(157)(158)(159)(160)(161)(162)(163)(164)(165)(166).…”

Section: The Cognitive Emotional and Behavior Cerebellummentioning

confidence: 99%

“…However, lesion studies have shown the involvement of cerebellum in dopamine deficit-related neurological and psychiatric disorders, such as Parkinson's disease, schizophrenia, autism spectrum disorders, and drug addiction (158)(159)(160)(161). Moreover, data coming from invasive studies in animal and tractography observation in humans revealed relevant patterns of intracerebellar dopaminergic connectivity, such as between the DN and the cerebellar cortex, and extrinsic interconnections between the cerebellum and traditional dopaminergic areas of the brain, including the midbrain, the neostriatum, the neocortex (162)(163)(164)(165). These connections could represent part of the cerebellar projective circuits which allow the cerebellum to contribute to motor and cognitive functions (164,166).…”

Section: The Cognitive Emotional and Behavior Cerebellummentioning

confidence: 99%

Networking of the Human Cerebellum: From Anatomo-Functional Development to Neurosurgical Implications

et al. 2022

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In the past, the cerebellum was considered to be substantially involved in sensory-motor coordination. However, a growing number of neuroanatomical, neuroimaging, clinical and lesion studies have now provided converging evidence on the implication of the cerebellum in a variety of cognitive, affective, social, and behavioral processes as well. These findings suggest a complex anatomo-functional organization of the cerebellum, involving a dense network of cortical territories and reciprocal connections with many supra-tentorial association areas. The final architecture of cerebellar networks results from a complex, highly protracted, and continuous development from childhood to adulthood, leading to integration between short-distance connections and long-range extra-cerebellar circuits. In this review, we summarize the current evidence on the anatomo-functional organization of the cerebellar connectome. We will focus on the maturation process of afferent and efferent neuronal circuitry, and the involvement of these networks in different aspects of neurocognitive processing. The final section will be devoted to identifying possible implications of this knowledge in neurosurgical practice, especially in the case of posterior fossa tumor resection, and to discuss reliable strategies to improve the quality of approaches while reducing postsurgical morbidity.

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Cerebellar Modulation of Mesolimbic Dopamine Transmission Is Functionally Asymmetrical

Cited by 21 publications

References 87 publications

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

The Cerebellar Dopaminergic System

Networking of the Human Cerebellum: From Anatomo-Functional Development to Neurosurgical Implications

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