Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice

Delgado-Zabalza, Lorena; Mallet, Nicolas P.; Glangetas, Christelle; Dabee, Guillaume; Garret, Maurice; Miguelez, Cristina; Baufreton, Jérôme

doi:10.1016/j.celrep.2023.113287

Cited by 7 publications

(9 citation statements)

References 81 publications

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“…We find that DLS projection neurons primarily synapse onto parvalbumin-expressing (PV + ) SNr neurons, whereas the DMS neurons primarily innervate non-parvalbumin-expressing (PV - ) SNr neurons. Our results agree with an enrichment of PV + neurons in the ventrolateral SNr 24,35 . Previous studies indicate that the second largest subpopulation of SNr neurons consists of GAD2 + /VGAT + /PV - neurons 13 or GAD2 + neurons 35 , and future studies will address whether DMS-targeted SNr neurons fall within this category.…”

Section: Discussionsupporting

confidence: 91%

“…Our results support previous findings indicating a medio-lateral gradient of intrinsic properties within the SNr, whereby medial neurons have higher R in and lower firing rates 13 . Similarly, our results agree with higher R in and lower baseline firing rate in PV - over PV + SNr neurons 24 . Synaptic facilitation may be required at DLS-SNr synapses to sustain postsynaptic responses in SNr neurons.…”

Section: Discussionsupporting

confidence: 90%

“…In a subset of these experiments, we used PVCre-TdTom mice to label parvalbumin-expressing (PV + ) SNr neurons, previously indicated as the major GABAergic subpopulation of the SNr 13,24 . We found a significantly higher proportion of TdTom - neurons (PV - ) among DMS-connected neurons (1 TdTom + , 10 TdTom - ) compared to a majority of TdTom + neurons (PV + ) among DLS-connected neurons (8 TdTom + , 2 TdTom - ) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Molecularly identified subpopulations of SNr neurons include a majority of parvalbumin (PV + ) expressing neurons, enriched in the ventrolateral aspects of the nucleus, as well as other subpopulations that have been characterized based on the expression of the vesicular GABA transporter (VGAT), calretinin (CR) and Glutamate Decarboxylase 2 enzyme (GAD2) 13,21–23 . The physiological properties and projection patterns of PV + SNr neurons distinguish them from other SNr neuron subpopulations 21,24 . The molecular and functional heterogeneity of SNr neurons is also tuned to the diversity of neuronal targets innervated by the SNr 13 .…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

“…How do arkypallidals integrate these disparate inputs and are there yet unknown afferents that remain to be discovered? Moreover, recent data suggest the possibility of heterogeneous neural subtypes within target nuclei of the GPe, setting up the possibility of a more complex collection of parallel pathways than those included in the classical basal ganglia model (Delgado-Zabalza et al, 2023). We are at the tip of the proverbial iceberg in terms of our understanding of this nucleus, and CBGT circuits more broadly.…”

Section: Looking Forwardmentioning

confidence: 99%

Rethinking the external globus pallidus and information flow in cortico-basal ganglia-thalamic circuits

Giossi,

Rubin,

Gittis

et al. 2024

Preprint

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For decades the external globus pallidus (GPe) has been viewed as a passive way-station in the indirect pathway of the cortico-basal ganglia-thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one-way descending striatal signals in the indirect pathway amplify the suppression of downstream thalamic nuclei by inhibiting GPe activity. Here we revisit this assumption, in light of new and emerging work on the cellular complexity, connectivity, and functional role of the GPe in behavior. We show how, according to this new circuit-level logic, the GPe is ideally positioned for relaying ascending and descending control signals within the basal ganglia. Focusing on the problem of inhibitory control, we illustrate how this bidirectional flow of information allows for the integration of reactive and proactive control mechanisms during action selection. Taken together, this new evidence points to the GPe as being a central hub in the CBGT circuit, participating in bidirectional information flow and linking multifaceted control signals to regulate behavior.

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Dopamine depletion weakens direct pathway modulation of SNr neurons

Aristieta,

Parker,

Gao

et al. 2024

Neurobiology of Disease

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Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice

Cited by 7 publications

References 81 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

Rethinking the external globus pallidus and information flow in cortico-basal ganglia-thalamic circuits

Dopamine depletion weakens direct pathway modulation of SNr neurons

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