Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons

Prager, Eric M.; Dorman, Daniel B.; Hobel, Zachary; Malgady, Jeffrey M; Blackwell, Kim T.; Plotkin, Joshua L.

doi:10.1016/j.neuron.2020.09.028

Cited by 34 publications

(32 citation statements)

References 94 publications

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“…In contrast to somatic excitability, dendritic excitability was exclusively enhanced in dSPNs. As all cortical inputs to SPNs target dendrites (Gerfen and Surmeier, 2011), and dendritic excitability profoundly shapes how SPNs respond to convergent corticostriatal inputs (Plotkin et al, 2011;Prager et al, 2020), this pathway-specific augmentation of dendritic excitability could help explain how cortically-evoked synaptic activity is biased towards the direct pathway in SAPAP3 KO mice (Ade et al, 2016). Why does deletion of a synaptic gene cause cell-wide changes in excitability?…”

Section: Discussionmentioning

confidence: 99%

Non-synaptic alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior

Malgady

Baez

Jimenez

et al. 2022

Preprint

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Deletion of the OCD-associated gene SAP90/PSD-95-associated protein 3 (Sapap3), which encodes a postsynaptic anchoring protein at corticostriatal synapses, causes OCD-like motor behaviors in mice. While corticostriatal synaptic dysfunction is central to this phenotype, the striatum efficiently adapts to pathological changes, often in ways that expand upon the original circuit impairment. Here we show that SAPAP3 deletion causes non-synaptic and pathway-specific alterations in dorsolateral striatum circuit function. While somatic excitability was elevated in striatal projection neurons (SPNs), dendritic excitability was exclusively enhanced in direct pathway SPNs. Layered on top of this, cholinergic modulation was altered in opposing ways: striatal cholinergic interneuron density and evoked acetylcholine release were elevated, while basal muscarinic modulation of SPNs was reduced. These data describe how SAPAP3 deletion alters the striatal landscape upon which impaired corticostriatal inputs will act, offering a basis for how pathological synaptic integration and unbalanced striatal output underlying OCD-like behaviors may be shaped.

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Section: Discussionmentioning

confidence: 99%

Non-synaptic alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior

Malgady

Baez

Jimenez

et al. 2022

Preprint

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“…4 a,c. Therefore, it is possible that the bifurcation in ADs may stem from differential dopamine dynamics, namely, differential electrically evoked dopamine release 113 , dopamine levels 114 , dopaminergic innervation 114 and modulation of state transitions in the striatal compartments 115 , and the preferential striosomal projection to dopaminergic neurons in substantia nigra pars compacta 116 . GABAergic and glutamatergic signaling were noted to be moderately influential in AD-SMI clustering (Fig.…”

Section: Discussionmentioning

confidence: 99%

Generalized and social anxiety disorder interactomes show distinctive overlaps with striosome and matrix interactomes

Karunakaran

Amemori

Ganapathiraju

et al. 2021

Sci Rep

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Mechanisms underlying anxiety disorders remain elusive despite the discovery of several associated genes. We constructed the protein–protein interaction networks (interactomes) of six anxiety disorders and noted enrichment for striatal expression among common genes in the interactomes. Five of these interactomes shared distinctive overlaps with the interactomes of genes that were differentially expressed in two striatal compartments (striosomes and matrix). Generalized anxiety disorder and social anxiety disorder interactomes showed exclusive and statistically significant overlaps with the striosome and matrix interactomes, respectively. Systematic gene expression analysis with the anxiety disorder interactomes constrained to contain only those genes that were shared with striatal compartment interactomes revealed a bifurcation among the disorders, which was influenced by the anterior cingulate cortex, nucleus accumbens, amygdala and hippocampus, and the dopaminergic signaling pathway. Our results indicate that the functionally distinct striatal pathways constituted by the striosome and the matrix may influence the etiological differentiation of various anxiety disorders.

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“…Our finding that plasticity at a single synapse is influenced by neighboring synaptic activity is consistent with many studies (both in vivo and in vitro) showing relationships between spatial synaptic input patterns and plasticity. For instance, in SPNs in vitro, spatially clustered synaptic inputs can produce supralinear depolarization (termed NMDA-spikes or plateau potentials) and synaptic calcium transients (Plotkin et al, 2011;Dorman et al, 2018;Prager et al, 2020;Du et al, 2017), and synaptic activation of 2-4 neighboring spines at depolarized potentials can produce nonlinear enhancement of spine calcium transients (Carter et al, 2007). Building on these findings, our work predicts that neighboring synaptic interactions can influence the direction and magnitude of corticostriatal synaptic plasticity in vivo, with high neighboring activity producing LTP and low neighbor- Observations suggest that functional synaptic clustering is a key component in plasticity and learning.…”

Section: Discussionmentioning

confidence: 99%

“…To investigate the effects of in vivo-like corticostriatal synaptic inputs on corticostriatal plasticity, we created a realistic biophysical SPN model (Prager et al, 2020) with a calcium-based plasticity rule (Jędrzejewska-Szmek et al, 2017) and simulated in vivo-like synaptic input patterns. The multicompartment, multi-ion channel model was optimized to fit electrophysiological data using an extended version of a parameter optimization algorithm we developed (Jȩ drzejewski- Dorman and Blackwell, 2021).…”

Section: Data-driven Spn Model Exhibits Calcium-based Synaptic Plasticity For In Vivo-like Inputsmentioning

confidence: 99%

Synaptic plasticity is predicted by spatiotemporal firing rate patterns and robust to in vivo-like variability

Dorman

Blackwell

2021

Preprint

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Synaptic plasticity, the experience-induced change in connections between neurons, underlies learning and memory in the brain. Most of our understanding of synaptic plasticity derives from in vitro experiments with precisely repeated stimulus patterns; however, neurons exhibit significant variability in vivo during repeated experiences. Further, the spatial pattern of synaptic inputs to the dendritic tree influences synaptic plasticity, yet is not considered in most synaptic plasticity rules. Here, we address the sensitivity of plasticity to trial-to-trial variability and delineate how spatiotemporal synaptic input patterns produce plasticity with in vivo-like conditions using a data-driven computational model with a calcium-based plasticity rule. Using in vivo spike train recordings as inputs, we show that plasticity is strongly robust to trial-to-trial variability of spike timing, and derive general synaptic plasticity rules describing how spatiotemporal patterns of synaptic inputs control the magnitude and direction of plasticity. Specifically, a high temporal input firing rate to a synapse late in a trial correlated with neighboring synaptic activity produces potentiation, while an earlier, moderate firing rate that is negatively correlated with neighboring synaptic activity produces depression. Together, our results reveal that calcium dynamics can unify diverse plasticity rules and reveal how spatiotemporal firing rate patterns control synaptic plasticity.

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Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons

Cited by 34 publications

References 94 publications

Non-synaptic alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior

Non-synaptic alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior

Generalized and social anxiety disorder interactomes show distinctive overlaps with striosome and matrix interactomes

Synaptic plasticity is predicted by spatiotemporal firing rate patterns and robust to in vivo-like variability

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