Exploring the role of striatal D1 and D2 medium spiny neurons in action selection using a virtual robotic framework

Bahuguna, Jyotika; Weidel, Philipp; Morrison, Abigail

doi:10.1111/ejn.14021

Cited by 17 publications

(11 citation statements)

References 60 publications

(118 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Still, this lack of effects may be seen as being at odds with previous models suggesting that striatal GABA plays a key role in integrating and selecting different downstream action requests (Bahuguna, Weidel, & Morrison, 2019; Buxton, Bracci, Overton, & Gurney, 2017; Tomkins et al, 2014). Similarly, previous studies proposed that event file coding depends on the striatum (Colzato et al, 2016; Persson et al, 2015).…”

Section: Discussionmentioning

confidence: 78%

On the functional role of striatal and anterior cingulateGABA+ in stimulus‐response binding

Takács

Stock

Kuntke

et al. 2021

Human Brain Mapping

View full text Add to dashboard Cite

Successful response selection relies on constantly updating stimulus–response associations. The Theory of Event Coding (TEC) proposes that perception and action are conjointly coded in event files, for which fronto‐striatal networks seem to play an important role. However, the exact neurobiochemical mechanism behind event file coding has remained unknown. We investigated the functional relevance of the striatal and anterior cingulate (ACC) GABAergic system using magnetic resonance spectroscopy (MRS). Specifically, the striatal and ACC concentrations of GABA+ referenced against N‐acetylaspartate (NAA) were assessed in 35 young healthy males, who subsequently performed a standard event file task. As predicted by the TEC, the participants' responses were modulated by pre‐established stimulus response bindings in event files. GABA+/NAA concentrations in the striatum and ACC were not correlated with the overall event binding effect. However, higher GABA+/NAA concentrations in the ACC were correlated with stronger event file binding processes in the early phase of the task. This association disappeared by the end of the task. Taken together, our findings show that striatal GABA+ levels does not seem to modulate event file binding, while ACC GABA+ seem to improve event file binding, but only as long as the participants have not yet gathered sufficient task experience. To the best of our knowledge, this is the first study providing direct evidence for the role of striatal and ACC GABA+ in stimulus–response bindings and thus insights into the brain structure‐specific neurobiological aspects of the TEC.

show abstract

Section: Discussionmentioning

confidence: 78%

On the functional role of striatal and anterior cingulateGABA+ in stimulus‐response binding

Takács

Stock

Kuntke

et al. 2021

Human Brain Mapping

View full text Add to dashboard Cite

show abstract

“…Normal striatal motor control requires activation of both direct and indirect SPNs population in a "complementary" and "coordinate" network dynamic (Jin et al, 2014;Klaus et al, 2017;Tecuapetla, Jin, Lima, & Costa, 2016;Vicente, Galvao-Ferreira, Tecuapetla, & Costa, 2016). Very recent results from a modeling study suggest that for planned movements both output pathways need to be engaged (Bahuguna, Weidel, & Morrison, 2018).…”

Section: Discussionmentioning

confidence: 99%

Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine‐depleted mice

Jáidar

Carrillo-Reid

Nakano

et al. 2019

Eur J of Neuroscience

View full text Add to dashboard Cite

For more than three decades it has been known, that striatal neurons become hyperactive after the loss of dopamine input, but the involvement of dopamine (DA) D1‐ or D2‐receptor‐expressing neurons has only been demonstrated indirectly. By recording neuronal activity using fluorescent calcium indicators in D1 or D2 eGFP‐expressing mice, we showed that following dopamine depletion, both types of striatal output neurons are involved in the large increase in neuronal activity generating a characteristic cell assembly of particular neurons that dominate the pattern. When we expressed channelrhodopsin in all the output neurons, light activation in freely moving animals, caused turning like that following dopamine loss. However, if the light stimulation was patterned in pulses the animals circled in the other direction. To explore the neuronal participation during this stimulation we infected normal mice with channelrhodopsin and calcium indicator in striatal output neurons. In slices made from these animals, continuous light stimulation for 15 s induced many cells to be active together and a particular dominant group of neurons, whereas light in patterned pulses activated fewer cells in more variable groups. These results suggest that the simultaneous activity of a large dominant group of striatal output neurons is intimately associated with parkinsonian symptoms.

show abstract

“…Conversely, indirect pathway MSNs (iMSNs) contain the D2 class of DA receptors, which are negatively coupled to PKA signaling. Activation of iMSNs inhibits inappropriate basal ganglia regulated motor function [42,43,44,45]. Thus, the opposing functions of dMSNs and iMSNs are, in part, regulated by post-synaptic responses to DA-dependent signaling.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of the Spinophilin Interactome in Rodent Striatum Following Psychostimulant Sensitization

et al. 2018

View full text Add to dashboard Cite

Glutamatergic projections from the cortex and dopaminergic projections from the substantia nigra or ventral tegmental area synapse on dendritic spines of specific GABAergic medium spiny neurons (MSNs) in the striatum. Direct pathway MSNs (dMSNs) are positively coupled to protein kinase A (PKA) signaling and activation of these neurons enhance specific motor programs whereas indirect pathway MSNs (iMSNs) are negatively coupled to PKA and inhibit competing motor programs. An imbalance in the activity of these two programs is observed following increased dopamine signaling associated with exposure to psychostimulant drugs of abuse. Alterations in MSN signaling are mediated by changes in MSN protein post-translational modifications, including phosphorylation. Whereas direct changes in specific kinases, such as PKA, regulate different effects observed in the two MSN populations, alterations in the specific activity of serine/threonine phosphatases, such as protein phosphatase 1 (PP1) are less well known. This lack of knowledge is due, in part, to unknown, cell-specific changes in PP1 targeting proteins. Spinophilin is the major PP1-targeting protein in striatal postsynaptic densities. Using proteomics and immunoblotting approaches along with a novel transgenic mouse expressing hemagglutainin (HA)-tagged spinophilin in dMSNs and iMSNs, we have uncovered cell-specific regulation of the spinophilin interactome following a sensitizing regimen of amphetamine. These data suggest regulation of spinophilin interactions in specific MSN cell types and may give novel insight into putative cell-specific, phosphatase-dependent signaling pathways associated with psychostimulants.

show abstract

Exploring the role of striatal D1 and D2 medium spiny neurons in action selection using a virtual robotic framework

Cited by 17 publications

References 60 publications

On the functional role of striatal and anterior cingulateGABA+ in stimulus‐response binding

On the functional role of striatal and anterior cingulateGABA+ in stimulus‐response binding

Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine‐depleted mice

Proteomic Analysis of the Spinophilin Interactome in Rodent Striatum Following Psychostimulant Sensitization

Contact Info

Product

Resources

About