scholarly journals Asymmetrical choice-related ensemble activity in direct and indirect-pathway striatal neurons drives perceptual decisions

2021 ◽  
Author(s):  
Lele Cui ◽  
Shunhang Tang ◽  
Kai Zhao ◽  
Jingwei Pan ◽  
Zhaoran Zhang ◽  
...  
Keyword(s):  
Decision Making ◽  
Action Selection ◽  
Behavioral Effects ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Two Photon ◽  
Decision Making Behavior ◽  
Ensemble Activity ◽  
Deep Brain

Action selection during decision-making depends on the basal ganglia circuits that comprise the direct and indirect pathways known to oppositely control movement. However, the mechanism for coordinating these opponent pathways during decision-making remains unclear. We address this by employing deep-brain two-photon imaging and optogenetic manipulations of the direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) in the posterior striatum during an auditory decision-making behavior. We show that while dSPNs and iSPNs play opposite causal roles during decision-making, each subtype contains divergent ensembles preferring different choices. The ensembles in dSPNs show stronger contralateral dominance than those in iSPNs manifested by higher-level activation and synchronization. Consistent with this asymmetrical contralateral dominance, optogenetic disinhibition of both pathways promoted contralateral choices. A computational model incorporating the striatal ensemble asymmetry recapitulated the causal behavioral effects. Our results uncover the asymmetry between opponent SPN ensembles as a circuit mechanism for action selection during decision-making.

scholarly journals Dopamine modulates the size of striatal projection neuron ensembles

2019 ◽  
Author(s):  
Marta Maltese ◽  
Jeffrey R. March ◽  
Alexander G. Bashaw ◽  
Nicolas X. Tritsch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Voluntary Movements ◽  
Indirect Pathway ◽  
Two Photon ◽  
Direct Pathway ◽  
Brain Circuits

SUMMARYDopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca2+ imaging to simultaneously monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that, contrary to prevailing models, DA does not modulate activity rates in either pathway strongly or differentially. Instead, DA exerts a prominent influence on the overall number of direct and indirect pathway SPNs recruited during behavior. Chronic loss of midbrain DA neurons in a model of Parkinson’s disease selectively impacts direct pathway ensembles and profoundly alters how they respond to DA elevation. Our results indicate that DA regulates striatal output by dynamically reconfiguring its sparse ensemble code and provide novel insights into the pathophysiology of Parkinson’s disease.

scholarly journals Cell type-specific membrane potential changes in dorsolateral striatum accompanying reward-based sensorimotor learning

Function ◽  
2021 ◽  
Author(s):  
Tanya Sippy ◽  
Corryn Chaimowitz ◽  
Sylvain Crochet ◽  
Carl C H Petersen
Keyword(s):  
Membrane Potential ◽  
Dopamine Receptors ◽  
Cell Types ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Cell Type Specific ◽  
Striatal Membrane ◽  
Sensory Evoked

Abstract The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, we investigated changes in membrane potential dynamics of dorsolateral striatal neurons comparing naïve mice and expert mice trained to lick a reward spout in response to whisker deflection. We recorded from three distinct cell types: i) direct pathway striatonigral neurons, which express type 1 dopamine receptors; ii) indirect pathway striatopallidal neurons, which express type 2 dopamine receptors; and iii) tonically active, putative cholinergic, striatal neurons. Task learning was accompanied by cell type-specific changes in the membrane potential dynamics evoked by the whisker deflection and licking in successfully-performed trials. Both striatonigral and striatopallidal types of striatal projection neurons showed enhanced task-related depolarization across learning. Striatonigral neurons showed a prominent increase in a short latency sensory-evoked depolarization in expert compared to naïve mice. In contrast, the putative cholinergic striatal neurons developed a hyperpolarizing response across learning, driving a pause in their firing. Our results reveal cell type-specific changes in striatal membrane potential dynamics across the learning of a simple goal-directed sensorimotor transformation, helpful for furthering the understanding of the various potential roles of different basal ganglia circuits.

scholarly journals Dopamine differentially modulates the size of projection neuron ensembles in the intact and dopamine-depleted striatum

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Marta Maltese ◽  
Jeffrey R March ◽  
Alexander G Bashaw ◽  
Nicolas X Tritsch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Population Level ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Voluntary Movements ◽  
Indirect Pathway ◽  
Two Photon ◽  
Brain Circuits

Dopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca2+ imaging to monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) simultaneously in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that increasing and decreasing DA biases striatal activity towards the direct and indirect pathways, respectively, by changing the overall number of SPNs recruited during behavior in a manner not predicted by existing models of DA function. This modulation is drastically altered in a model of Parkinson's disease. Our results reveal a previously unappreciated population-level influence of DA on striatal output and provide novel insights into the pathophysiology of Parkinson's disease.

Interaction between cognitive and motor cortico-basal ganglia loops during decision making: a computational study

2013 ◽  
Vol 109 (12) ◽  
pp. 3025-3040 ◽  
Author(s):  
M. Guthrie ◽  
A. Leblois ◽  
A. Garenne ◽  
T. Boraud
Keyword(s):  
Decision Making ◽  
Basal Ganglia ◽  
Computational Study ◽  
Selection Process ◽  
Action Selection ◽  
External Input ◽  
Projection Neurons ◽  
Cognitive Level ◽  
Striatal Projection Neurons ◽  
Previous Modeling Study

In a previous modeling study, Leblois et al. (2006) demonstrated an action selection mechanism in cortico-basal ganglia loops based on competition between the positive feedback, direct pathway through the striatum and the negative feedback, hyperdirect pathway through the subthalamic nucleus. The present study investigates how multiple level action selection could be performed by the basal ganglia. To do this, the model is extended in a manner consistent with known anatomy and electrophysiology in three main areas. First, two-level decision making has been incorporated, with a cognitive level selecting based on cue shape and a motor level selecting based on cue position. We show that the decision made at the cognitive level can be used to bias the decision at the motor level. We then demonstrate that, for accurate transmission of information between decision-making levels, low excitability of striatal projection neurons is necessary, a generally observed electrophysiological finding. Second, instead of providing a biasing signal between cue choices as an external input to the network, we show that the action selection process can be driven by reasonable levels of noise. Finally, we incorporate dopamine modulated learning at corticostriatal synapses. As learning progresses, the action selection becomes based on learned visual cue values and is not interfered with by the noise that was necessary before learning.

scholarly journals Spatial organization of functional clusters representing reward and movement information in the striatal direct and indirect pathways

2020 ◽  
Vol 117 (43) ◽  
pp. 27004-27015
Author(s):  
Jung Hwan Shin ◽  
Min Song ◽  
Se-Bum Paik ◽  
Min Whan Jung
Keyword(s):  
Classical Conditioning ◽  
Spatial Organization ◽  
Movement Control ◽  
Striatal Neurons ◽  
Spatial Clusters ◽  
Indirect Pathway ◽  
Free Exploration ◽  
Neural Processes ◽  
A2a Receptor ◽  
Ensemble Activity

To obtain insights into striatal neural processes underlying reward-based learning and movement control, we examined spatial organizations of striatal neurons related to movement and reward-based learning. For this, we recorded the activity of direct- and indirect-pathway neurons (D1 and A2a receptor-expressing neurons, respectively) in mice engaged in probabilistic classical conditioning and open-field free exploration. We found broadly organized functional clusters of striatal neurons in the direct as well as indirect pathways for both movement- and reward-related variables. Functional clusters for different variables were partially overlapping in both pathways, but the overlap between outcome- and value-related functional clusters was greater in the indirect than direct pathway. Also, value-related spatial clusters were progressively refined during classical conditioning. Our study shows the broad and learning-dependent spatial organization of functional clusters of dorsal striatal neurons in the direct and indirect pathways. These findings further argue against the classic model of the basal ganglia and support the importance of spatiotemporal patterns of striatal neuronal ensemble activity in the control of behavior.

scholarly journals Choice suppression is achieved through opponent but not independent function of the striatal indirect pathway in mice

2019 ◽  
Author(s):  
Kristen Delevich ◽  
Benjamin Hoshal ◽  
Anne GE Collins ◽  
Linda Wilbrecht
Keyword(s):  
Action Selection ◽  
Projection Neurons ◽  
Independent Function ◽  
Indirect Pathway ◽  
Successful Design ◽  
Freely Moving ◽  
Foraging Task ◽  
Simple Fashion ◽  
Dorsomedial Striatum

AbstractThe dorsomedial striatum (DMS) plays a key role in action selection, but little is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs) contribute to choice suppression in freely moving animals. Here, we used pathway-specific chemogenetic manipulation during a serial choice foraging task to test opposing predictions for iSPN function generated by two theories: 1) the ‘select/suppress’ heuristic which suggests iSPN activity is required to suppress alternate choices and 2) the network-inspired Opponent Actor Learning model (OpAL) which proposes that the weighted difference of dSPN and iSPN activity determines choice. We found that chemogenetic activation, but not inhibition, of iSPNs disrupted learned suppression of nonrewarded choices, consistent with the predictions of the OpAL model. Our findings suggest that iSPNs’ role in stopping and freezing does not extend in a simple fashion to choice suppression. These data may provide insights critical for the successful design of interventions for addiction or other conditions in which suppression of behavior is desirable.

scholarly journals Striatal Control of Movement: A Role for New Neuronal (Sub-) Populations?

2021 ◽  
Vol 15 ◽  
Author(s):  
Tim Fieblinger
Keyword(s):  
Brain Area ◽  
Projection Neurons ◽  
Anatomical Location ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Transcriptional Profiles ◽  
Transcriptional Signature ◽  
Neuronal Populations ◽  
Abnormal Movements ◽  
Two Populations

The striatum is a very heterogenous brain area, composed of different domains and compartments, albeit lacking visible anatomical demarcations. Two populations of striatal spiny projection neurons (SPNs) build the so-called direct and indirect pathway of the basal ganglia, whose coordinated activity is essential to control locomotion. Dysfunction of striatal SPNs is part of many movement disorders, such as Parkinson’s disease (PD) and L-DOPA-induced dyskinesia. In this mini review article, I will highlight recent studies utilizing single-cell RNA sequencing to investigate the transcriptional profiles of striatal neurons. These studies discover that SPNs carry a transcriptional signature, indicating both their anatomical location and compartmental identity. Furthermore, the transcriptional profiles reveal the existence of additional distinct neuronal populations and previously unknown SPN sub-populations. In a parallel development, studies in rodent models of PD and L-DOPA-induced dyskinesia (LID) report that direct pathway SPNs do not react uniformly to L-DOPA therapy, and that only a subset of these neurons is underlying the development of abnormal movements. Together, these studies demonstrate a new level of cellular complexity for striatal (dys-) function and locomotor control.

scholarly journals Distinct roles of striatal direct and indirect pathways in value-based decision making

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shinae Kwak ◽  
Min Whan Jung
Keyword(s):  
Decision Making ◽  
Choice Behavior ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Impaired Performance ◽  
Reversal Frequency ◽  
Value Learning ◽  
Model Based Analysis

The striatum is critically involved in value-based decision making. However, it is unclear how striatal direct and indirect pathways work together to make optimal choices in a dynamic and uncertain environment. Here, we examined the effects of selectively inactivating D1 receptor (D1R)- or D2 receptor (D2R)-expressing dorsal striatal neurons (corresponding to direct- and indirect-pathway neurons, respectively) on mouse choice behavior in a reversal task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Inactivation of either D1R- or D2R-expressing striatal neurons impaired performance in both tasks, but the pattern of altered choice behavior differed between the two animal groups. A reinforcement learning model-based analysis indicated that inactivation of D1R- and D2R-expressing striatal neurons selectively impairs value-dependent action selection and value learning, respectively. Our results suggest differential contributions of striatal direct and indirect pathways to two distinct steps in value-based decision making.

scholarly journals Mutant huntingtin enhances activation of dendritic Kv4 K+ channels in striatal spiny projection neurons

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Luis Carrillo-Reid ◽  
Michelle Day ◽  
Zhong Xie ◽  
Alexandria E Melendez ◽  
Jyothisri Kondapalli ◽  
...  
Keyword(s):  
Zinc Finger Protein ◽  
Ex Vivo ◽  
Brain Slices ◽  
Projection Neurons ◽  
Receptor Signaling ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Trkb Receptor ◽  
Dendritic Excitability ◽  
Kv4 Channels

Huntington’s disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued by knocking-down expression of Kv4 channels, by disrupting KChIP binding, by restoring TrkB receptor signaling or by lowering mutant-Htt (mHtt) levels with a zinc finger protein. Collectively, these studies demonstrate that mHtt induces reversible alterations in the dendritic excitability of iSPNs that could contribute to the motor symptoms of HD.

scholarly journals Cell-type and subcellular compartment-specific APEX2 proximity labeling reveals activity-dependent nuclear proteome dynamics in the striatum

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
V. Dumrongprechachan ◽  
R. B. Salisbury ◽  
G. Soto ◽  
M. Kumar ◽  
M. L. MacDonald ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Functional Organization ◽  
Projection Neurons ◽  
Specific Information ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Subcellular Compartment ◽  
Cell Type Specific ◽  
And Function

AbstractThe vertebrate brain consists of diverse neuronal types, classified by distinct anatomy and function, along with divergent transcriptomes and proteomes. Defining the cell-type specific neuroproteomes is important for understanding the development and functional organization of neural circuits. This task remains challenging in complex tissue, due to suboptimal protein isolation techniques that often result in loss of cell-type specific information and incomplete capture of subcellular compartments. Here, we develop a genetically targeted proximity labeling approach to identify cell-type specific subcellular proteomes in the mouse brain, confirmed by imaging, electron microscopy, and mass spectrometry. We virally express subcellular-localized APEX2 to map the proteome of direct and indirect pathway spiny projection neurons in the striatum. The workflow provides sufficient depth to uncover changes in the proteome of striatal neurons following chemogenetic activation of Gαq-coupled signaling cascades. This method enables flexible, cell-type specific quantitative profiling of subcellular proteome snapshots in the mouse brain.

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