A non-canonical striatopallidal “Go” pathway that supports motor control

Labouesse, Marie A.; Torres-Herraez, Arturo; Chohan, Muhammad O.; Villarin, Joseph M.; Greenwald, Julia E.; Sun, Xiaoxiao; Zahran, Mysarah; Tang, Alice; Lam, Sherry; Veenstra‐VanderWeele, Jeremy; Lacefield, Clay; Bonaventura, Jordi; Michaelides, Michael; Chan, C. Savio; Kellendonk, Christoph

doi:10.21203/rs.3.rs-2524816/v1

Cited by 4 publications

(4 citation statements)

References 87 publications

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“…supp. 3C), in agreement with what previously observed in vivo at dSPN-GPe bridge collateral terminals 36 . 6-7 days after withdrawal, AIR (Cre-, Cre+) and CIE (Cre-, Cre+) mice underwent operant conditioning for 20% sucrose reward that began with 5 days of fixed ratio 1 training and then progressed to 2 days of random ratio 10 and 4 days of random ratio 20 training (Fig.…”

Section: Resultssupporting

confidence: 91%

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Sitzia,

Bariselli,

Gracias

et al. 2023

Preprint

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While cortico-striatal circuit deficits contribute to Alcohol Use Disorder, the impact of alcohol on synaptic function in the basal ganglia output, the substantia nigra pars reticulata (SNr), remains unclear. Here, we found that the inputs from the dorsomedial (DMS) and dorsolateral striatum (DLS) differ in their presynaptic properties and target molecularly distinct subpopulations of SNr neurons. We also discovered that indirect pathway subthalamic (STN) inputs to the medial and lateral SNr have different presynaptic properties and that STN inputs are stronger in the lateral SNr. Chronic alcohol exposure (CIE) potentiated DLS inputs but did not affect the strength and presynaptic release properties of DMS and subthalamic inputs to SNr neurons. Chemogenetic inhibition of DLS direct pathway projection neurons impaired action performance in an operant conditioning task in CIE mice but not control mice. Overall, our work identifies a synaptic mechanism whereby chronic alcohol induces a gain of function for action control in direct pathway neurons in the dorsolateral striatum.TeaserChronic alcohol selectively potentiates DLS synaptic inputs to the SNr, enhancing their role in action control.

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Section: Resultssupporting

confidence: 91%

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Sitzia,

Bariselli,

Gracias

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The activation of hM4D(Gi) by clozapine- N -oxide (CNO) decreased GABA release at striatonigral inputs (fig. S3C), in agreement with what previously observed in vivo at dSPN-GPe bridge collateral terminals ( 35 ). Six to 7 days after withdrawal, AIR (Cre − and Cre + ) and CIE (Cre − and Cre + ) mice underwent operant conditioning for 20% sucrose reward that began with training for 5 days of fixed ratio of 1 and then progressed to training for 2 days of RR 10 and 4 days of RR 20 (Fig.…”

Section: Resultssupporting

confidence: 91%

Chronic alcohol induces subcircuit-specific striatonigral plasticity enhancing the sensorimotor basal ganglia role in action execution

Sitzia,

Bariselli,

Gracias

et al. 2024

Sci. Adv.

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Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic function and neuronal excitability in the dorsal striatum, but it remains unclear how it affects BG output that is mediated by the substantia nigra pars reticulata (SNr). Here, we describe a neuronal subpopulation-specific synaptic organization of striatal and subthalamic (STN) inputs to the medial and lateral SNr. Chronic alcohol exposure (CIE) potentiated dorsolateral striatum (DLS) inputs but did not change dorsomedial striatum and STN inputs to the SNr. Chemogenetic inhibition of DLS direct pathway neurons revealed an enhanced role for DLS direct pathway neurons in execution of an instrumental lever-pressing task. Overall, we reveal a subregion-specific organization of striatal and subthalamic inputs onto the medial and lateral SNr and find that potentiated DLS-SNr inputs are accompanied by altered BG control of action execution following CIE.

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“…A GPe-to-SNpc connection has been demonstrated electrophysiologically, without specification of its topographic origins within GPe 35,36 . The clarity of the GPe core-periphery distinction found here and in these previous studies is particularly notable given the high degree of collateralization of striatal projections to the GPe 7,21,25,29,37–41 .…”

Section: Resultssupporting

confidence: 70%

“…These DMS-DLS differences extend much pivotal previous work on differences between signaling in the DMS and DLS neurons unmarked with respect to their striosomal or matrix origins [81][82][83][84][85][86][87][88][89] , thus indicating that topographic constraints are a general feature of striatal circuits. Our findings also extend pioneering efforts to identify functional characteristics of D1 and D2 neurons in the striatum 41,83,86,98,106 . Our work builds on these and other studies.…”

Section: Effects Of the S-d1 And S-d2 Pathways On Dopamine Release In...supporting

confidence: 73%

Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems

Lazaridis,

Crittenden,

Ahn

et al. 2024

Preprint

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The classic output pathways of the basal ganglia are known as the direct-D1 and indirect-D2, or “Go/No-Go”, pathways. Balance of the activity in these canonical direct-indirect pathways is considered a core requirement for normal movement control, and their imbalance is a major etiologic factor in movement disorders including Parkinson’s disease. We present evidence for a conceptually equivalent parallel system of direct-D1 and indirect-D2 pathways that arise from striatal projection neurons (SPNs) of the striosome compartment rather than from the matrix. These striosomal direct (S-D1) and indirect (S-D2) pathways, as a pair, target dopamine-containing neurons of the substantia nigra (SNpc) instead of the motor output nuclei of the basal ganglia. The novel anatomically and functionally distinct indirect-D2 striosomal pathway targets dopaminergic SNpc cells indirectly via a core region of the external pallidum (GPe). We demonstrate that these S-D1 and S-D2 pathways oppositely modulate striatal dopamine release in freely behaving mice under open-field conditions and oppositely modulate locomotor and other movements. These S-D1 and S-D2 pathways further exhibit different, time-dependent responses during performance of a probabilistic decision-making maze task and respond differently to rewarding and aversive stimuli. These contrasts depend on mediolateral and anteroposterior striatal locations of the SPNs as are the classic direct and indirect pathways. The effects of S-D1 and S-D2 stimulation on striatal dopamine release and voluntary locomotion are nearly opposite. The parallelism of the direct-indirect circuit design motifs of the striosomal S-D and S-D2 circuits and canonical matrix M-D1 and M-D2, and their contrasting behavioral effects, call for a major reformulation of the classic direct-indirect pathway model of basal ganglia function. Given that some striosomes receive limbic and association cortical inputs, the S-D1 and S-D2 circuits likely influence motivation for action and behavioral learning, complementing and possibly reorienting the motoric activities of the canonical matrix pathways. At a fundamental level, these findings suggest a unifying framework for aligning two sets of circuits that share the organizational motif of opponent D1 and D2 regulation, but that have different outputs and can even have opposite polarities in their targets and effects, albeit conditioned by striatal topography. Our findings further delineate a potentially therapeutically important set of pathways influencing dopamine, including a D2 receptor-linked S-D2 pathway likely unknowingly targeted by administration of many therapeutic drugs including those for Parkinson’s disease. The novel parallel pathway model that we propose here could help to account for the normally integrated modulatory influence of the basal ganglia on motivation for actions as well as the actions themselves.HIGHLIGHTS∎Direct-D1 and Indirect-D2 striosomal pathways (S-D1, S-D2) target SNpc dopamine cells∎The S-D2 circuit targets a distinct central zone of the external pallidum (cGPe)∎Stimulation of S-D2 increases, of S-D1 decreases, striatal dopamine and movement∎Activity of S-D1 increases, of S-D2 decreases, at outcome; S-D1 activity brackets task

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A non-canonical striatopallidal “Go” pathway that supports motor control

Cited by 4 publications

References 87 publications

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

Chronic alcohol induces subcircuit-specific striatonigral plasticity enhancing the sensorimotor basal ganglia role in action execution

Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems

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