Widespread inhibitory projections from the cerebellar interposed nucleus

Judd, Elena N.; Lewis, Samantha M.; Heck, Daniel Glenn; Person, Abigail L.

doi:10.1101/2020.12.31.425011

Cited by 3 publications

(4 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of the CB to derive a complex repertoire of non-motor functions from its relatively invariant cellular organization is largely attributed to its diverse outputs [35][36][37][38] . In addition to the heavily emphasized non-motor cerebellar influences on cortical regions [39][40][41][42][43][44][45] , functional and/or anatomical cerebellar connections with subcortical structures critical for cognition and emotion have also been documented 37,[46][47][48][49][50] .…”

Section: Introductionmentioning

confidence: 99%

“…The ability of the CB to derive a complex repertoire of non-motor functions from its relatively invariant cellular organization is largely attributed to its diverse outputs (Reeber et al, 2013;Xiao and Scheiffele, 2018;Fujita et al, 2020;Judd et al, 2021). In addition to the heavily emphasized non-motor cerebellar influences on cortical regions (Ito, 2008;Mittleman et al, 2008;Strick et al, 2009;Watson et al, 2014;Gao et al, 2018;Brady et al, 2019;Kelly et al, 2020), functional and/or anatomical cerebellar connections with subcortical structures that are critical for cognition and emotion have also been documented (Snider and Maiti, 1976;Heath et al, 1978;Dietrichs and Haines, 1989;Rochefort et al, 2011;Fujita et al, 2020;Zeidler et al, 2020;Jung et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

D’Ambra

Jung

Ganesan

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

D’Ambra

Jung

Ganesan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

D’Ambra

Vlasov

Jung

et al. 2023

Preprint

View full text Add to dashboard Cite

Although the cerebellum is now recognized as part of a long-range brain network that serves limbic functions and motivated behavior, knowledge of cerebello-limbic connectivity is limited, and nothing is known about how the cerebellum connects functionally to the nucleus accumbens (NAc). Here, we report that stimulation of cerebellar nuclei in mice of both sexes modulates spiking activity in both NAc core and medial shell with fast excitation and slower, less synchronized inhibition. Fast responses would be well poised to support rapid communication of information critical to the control of motivated behavior, whereas slower responses may be suggestive of a regulatory function, such as gain control. Tracing experiments to chart cerebellar nuclei-NAc pathways identified disynaptic pathways that recruit the ventral tegmental area (VTA) and intralaminar thalamus (Centromedial and Parafascicular nuclei) as intermediary nodes. Optogenetic activation of cerebellar axons in each of these nodes was sufficient to evoke responses in both NAc core and medial shell, albeit with distinct, node-dependent properties. These pathways and the functional connectivity they support could underlie the role of the cerebellum in motivated behavior.

show abstract

“…Although the cerebellum is well known to play a crucial role in fine movement and motor activity ( Ito, 1984 ), recent evidence suggest that the cerebellum is increasingly implicated in a variety of brain functions, including reward prediction ( Wagner et al, 2017 ; Heffley et al, 2018 ; Carta et al, 2019 ; Kostadinov et al, 2019 ), motor planning ( Gao et al, 2018 ; Chabrol et al, 2019 ; Wagner et al, 2019 ), and higher cognitive functions such as language and social behavior ( Fiez and Petersen, 1998 ; Van Overwall et al, 2014 ; Schmahmann et al, 2019 ). Although the novel neural connections between the cerebellum and other brain areas and individual cellular elements are being unveiled rapidly ( Judd et al, 2020 ; Kebschull et al, 2020 ; Kozareva et al, 2020 ), to achieve a comprehensive understanding of cerebellar functions, characterization of synaptic transmission and modulatory actions on neuronal and synaptic factors in the cerebellum is required. Inhibitory GABAergic transmission from Purkinje cells (PCs), the sole output neuron of the cerebellar cortex, has not been fully understood.…”

Section: Introductionmentioning

confidence: 99%

Modulatory Effects of Monoamines and Perineuronal Nets on Output of Cerebellar Purkinje Cells

Hirono

Karube

Yanagawa

2021

Front. Neural Circuits

View full text Add to dashboard Cite

Classically, the cerebellum has been thought to play a significant role in motor coordination. However, a growing body of evidence for novel neural connections between the cerebellum and various brain regions indicates that the cerebellum also contributes to other brain functions implicated in reward, language, and social behavior. Cerebellar Purkinje cells (PCs) make inhibitory GABAergic synapses with their target neurons: other PCs and Lugaro/globular cells via PC axon collaterals, and neurons in the deep cerebellar nuclei (DCN) via PC primary axons. PC-Lugaro/globular cell connections form a cerebellar cortical microcircuit, which is driven by serotonin and noradrenaline. PCs’ primary outputs control not only firing but also synaptic plasticity of DCN neurons following the integration of excitatory and inhibitory inputs in the cerebellar cortex. Thus, strong PC-mediated inhibition is involved in cerebellar functions as a key regulator of cerebellar neural networks. In this review, we focus on physiological characteristics of GABAergic transmission from PCs. First, we introduce monoaminergic modulation of GABAergic transmission at synapses of PC-Lugaro/globular cell as well as PC-large glutamatergic DCN neuron, and a Lugaro/globular cell-incorporated microcircuit. Second, we review the physiological roles of perineuronal nets (PNNs), which are organized components of the extracellular matrix and enwrap the cell bodies and proximal processes, in GABA release from PCs to large glutamatergic DCN neurons and in cerebellar motor learning. Recent evidence suggests that alterations in PNN density in the DCN can regulate cerebellar functions.

show abstract

Widespread inhibitory projections from the cerebellar interposed nucleus

Cited by 3 publications

References 101 publications

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

Modulatory Effects of Monoamines and Perineuronal Nets on Output of Cerebellar Purkinje Cells

Contact Info

Product

Resources

About