Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

Deffains, Marc; Iskhakova, Liliya; Katabi, Shiran; Haber, Suzanne N.; Israel, Zvi; Bergman, Hagai

doi:10.7554/elife.16443

Cited by 103 publications

(143 citation statements)

References 112 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…as in consolidation processes). This suggestion is in line with studies showing that the striatum maintains intermediate representations, potentially via sustained activity [60], to allow learning that combines reinforcement and memory under spaced conditions [61,62].…”

Section: Resultssupporting

confidence: 86%

A geometric representation unveils learning dynamics in primate neurons

Cohen

Schneidman

2019

Preprint

View full text Add to dashboard Cite

Primates can quickly and advantageously adopt complex rule-based behaviors. We studied acquisition of rule-based classification while recording single neurons in the dorsal-anteriorcingulate-cortex (dACC) and the Striatum. Monkeys performed trial-by-trial classification on a rich set of multi-cue patterns, allowing de-novo rule-learning with varying conceptual complexities every few days. To examine neural dynamics during the learning itself, we represent each rule with a spanning set of the space formed by the stimulus features. Because neural preference can be expressed by feature combinations, we can track neural dynamics in geometrical terms in this space, allowing a compact universal description of neural trajectories by observing changes in either vector-magnitude and/or angle-to-rule. We find that a large fraction of cells in both regions follow the behavior during learning. Neurons in the dACC mainly rotate towards the rule, suggesting an increase in selectivity that approximates the rule; whereas in the Putamen we additionally find a prominent magnitude increase, suggesting strengthening of confidence. Moreover, magnitude increases in the striatum followed rotation in the dACC, and finally, the neural policy at the end of the session predicted next-day behavior. Using this novel framework enables tracking of neural dynamics during learning and suggests differential roles of confidence and policy for the different brain regions.

show abstract

Section: Resultssupporting

confidence: 86%

A geometric representation unveils learning dynamics in primate neurons

Cohen

Schneidman

2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Increased synchrony and neural oscillations in the STN and GPi have been observed in primate (Albin et al, 1989; Bergman et al, 1994; Nini et al, 1995) and rodent (Costa et al, 2006; Magill et al, 2001) models of PD. It has also been shown that STN activity correlates with downstream basal ganglia activity in PD monkeys (Deffains et al, 2016). Although the causal link between STN oscillations and PD symptoms remain elusive (Kuhn et al, 2009; Weinberger et al, 2009), it has been shown that pathological oscillations are suppressed by volitional movement (Amirnovin et al, 2004), dopamine replacement therapy (Brown et al, 2001; Levy et al, 2002; Priori et al, 2004; Weinberger et al, 2009), and STN-DBS therapy (Kuhn et al, 2008; Wingeier et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Studying Brain Circuit Function with Dynamic Causal Modeling for Optogenetic fMRI

Bernal-Casas

Lee

Weitz

et al. 2017

Neuron

View full text Add to dashboard Cite

Summary Defining the large-scale behavior of brain circuits with cell type specificity is a major goal of neuroscience. However, neuronal circuit diagrams typically draw upon anatomical and electrophysiological measurements acquired in isolation. Consequently, a dynamic and cell type-specific connectivity map has never been constructed from simultaneous measurements across the brain. Here, we introduce dynamic causal modeling (DCM) for optogenetic fMRI experiments – which uniquely allow cell type-specific, brain-wide functional measurements – to parameterize the causal relationships among regions of a distributed brain network with cell type specificity. Strikingly, when applied to the brain-wide basal ganglia-thalamocortical network, DCM accurately reproduced the empirically observed time series, and the strongest connections were key connections of optogenetically stimulated pathways. We predict that quantitative and cell type-specific descriptions of dynamic connectivity, as illustrated here, will empower novel systems-level understanding of neuronal circuit dynamics and facilitate the design of more effective neuromodulation therapies.

show abstract

“…Most evidence for increased iMSN activity in parkinsonism is indirect, based on downstream basal ganglia nuclei (Bergman et al, 1994; Filion and Tremblay, 1991; Galvan et al, 2015; Soares et al, 2004) in restrained nonhuman primates. These nuclei, however, integrate striatal and extrastriatal inputs; the latter perhaps more important for shaping output (Deffains et al, 2016). In anesthetized parkinsonian rodents, one recent study of identified iMSNs found no change in firing rate (Ketzef et al, 2017), while an older study of putative iMSNs showed a very modest increase (0.5 spikes/s) in the firing rate (Mallet et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Aberrant Striatal Activity in Parkinsonism and Levodopa-Induced Dyskinesia

Ryan¹,

2018

View full text Add to dashboard Cite

Action selection relies on the coordinated activity of striatal direct and indirect pathway medium spiny neurons (dMSNs and iMSNs, respectively). Loss of dopamine in Parkinson's disease is thought to disrupt this balance. While dopamine replacement with levodopa may restore normal function, the development of involuntary movements (levodopa-induced dyskinesia [LID]) limits therapy. How chronic dopamine loss and replacement with levodopa modulate the firing of identified MSNs in behaving animals is unknown. Using optogenetically labeled striatal single-unit recordings, we assess circuit dysfunction in parkinsonism and LID. Counter to current models, we found that following dopamine depletion, iMSN firing was elevated only during periods of immobility, while dMSN firing was dramatically and persistently reduced. Most notably, we identified a subpopulation of dMSNs with abnormally high levodopa-evoked firing rates, which correlated specifically with dyskinesia. These findings provide key insights into the circuit mechanisms underlying parkinsonism and LID, with implications for developing targeted therapies.

show abstract

Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

Cited by 103 publications

References 112 publications

A geometric representation unveils learning dynamics in primate neurons

A geometric representation unveils learning dynamics in primate neurons

Studying Brain Circuit Function with Dynamic Causal Modeling for Optogenetic fMRI

Aberrant Striatal Activity in Parkinsonism and Levodopa-Induced Dyskinesia

Contact Info

Product

Resources

About