scholarly journals Cyclic AMP-producing chemogenetic activation of indirect pathway striatal projection neurons and the downstream effects on the globus pallidus and subthalamic nucleus in freely moving mice

2018 ◽  
Vol 145 (6) ◽  
pp. 436-448 ◽  
Author(s):  
Safa Bouabid ◽  
Fu-Ming Zhou
Keyword(s):  
Cyclic Amp ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Downstream Effects ◽  
Striatal Projection Neurons ◽  
Freely Moving

scholarly journals Differential Synaptic Input to External Globus Pallidus Neuronal Subpopulations In Vivo

2020 ◽  
Author(s):  
Maya Ketzef ◽  
Gilad Silberberg
Keyword(s):  
Globus Pallidus ◽  
Synaptic Input ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Inhibitory Input ◽  
Indirect Pathway ◽  
Functional Roles ◽  
Striatal Projection Neurons ◽  
Afferent Inputs

SummaryThe rodent external Globus Pallidus (GPe) contains two main neuronal subpopulations, prototypic and arkypallidal cells, which differ in their cellular properties. Their functional synaptic connectivity is, however, largely unknown. Here, we studied the membrane properties and synaptic inputs to these subpopulations in the mouse GPe. We obtained in vivo whole-cell recordings from identified GPe neurons and used optogenetic stimulation to dissect their afferent inputs from the striatum and subthalamic nucleus (STN). All GPe neurons received barrages of excitatory and inhibitory input during slow wave activity. The modulation of their activity was cell-type specific and shaped by their respective membrane properties and afferent inputs. Both GPe subpopulations received synaptic input from STN and striatal projection neurons (MSNs). STN and indirect pathway MSNs strongly targeted prototypic cells while direct pathway MSNs selectively inhibited arkypallidal cells. We show that GPe subtypes are differently embedded in the basal ganglia network, supporting distinct functional roles.

scholarly journals Dysregulation of external globus pallidus-subthalamic nucleus network dynamics in Parkinsonian mice

2019 ◽  
Author(s):  
Ryan F. Kovaleski ◽  
Joshua W. Callahan ◽  
Marine Chazalon ◽  
Jérôme Baufreton ◽  
Mark D. Bevan
Keyword(s):  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Wave Activity ◽  
Motor Dysfunction ◽  
Network Activity ◽  
Projection Neurons ◽  
D2 Dopamine Receptor ◽  
Striatal Projection Neurons ◽  
Cell Class ◽  
Compensatory Plasticity

AbstractReciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN) neurons form a key, centrally-positioned network within the basal ganglia, a group of subcortical brain nuclei critical for voluntary movement. In Parkinson’s disease (PD) and its models, abnormal rates and patterns of GPe-STN network activity are linked to motor dysfunction. Using cell class-specific optogenetic identification and inhibition approaches during cortical slow-wave activity and activation, we report that in dopamine-depleted mice 1) D2 dopamine receptor expressing striatal projection neurons (D2-SPNs) are hyperactive 2) prototypic parvalbumin (PV)-expressing GPe neurons are excessively patterned by D2-SPNs 3) despite being disinhibited, STN neurons are not hyperactive 4) the STN opposes rather than facilitates abnormal striatopallidal patterning. Together with recent studies, these data argue that in Parkinsonian mice abnormal, temporally offset PV GPe neuron and STN activity results from increased striatopallidal transmission and that compensatory plasticity within the STN prevents its hyperactivity.

Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method

2014 ◽  
Vol 112 (1) ◽  
pp. 120-146 ◽  
Author(s):  
Kenji Morita
Keyword(s):  
D2 Receptor ◽  
Computational Method ◽  
Cortical Activation ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Short Term ◽  
Apparent Contradiction ◽  
Striatal Projection Neurons ◽  
Cortical Inputs ◽  
Stimulation Of

The corticostriatal system is considered to be crucially involved in learning and action selection. Anatomical studies have shown that two types of corticostriatal neurons, intratelencephalic (IT) and pyramidal tract (PT) cells, preferentially project to dopamine D1 or D2 receptor-expressing striatal projection neurons, respectively. In contrast, an optogenetic study has shown that stimulation of IT axons evokes comparable responses in D1 and D2 cells and that stimulation of PT axons evokes larger responses in D1 cells. Since the optogenetic study applied brief stimulation only, however, the overall impacts of repetitive inputs remain unclear. Moreover, the apparent contradiction between the anatomical and optogenetic results remains to be resolved. I addressed these issues by using a computational approach. Specifically, I constructed a model of striatal response to cortical inputs, with parameters regarding short-term synaptic plasticity and anatomical connection strength for each connection type. Under the constraint of the optogenetic results, I then explored the parameters that best explain the previously reported paired-pulse ratio of response in D1 and D2 cells to cortical and intrastriatal stimulations, which presumably recruit different compositions of IT and PT fibers. The results indicate that 1) IT→D1 and PT→D2 connections are anatomically stronger than IT→D2 and PT→D1 connections, respectively, consistent with the previous findings, and that 2) IT→D1 and PT→D2 synapses entail short-term facilitation, whereas IT→D2 and PT→D1 synapses would basically show depression, and thereby 3) repetitive IT or PT inputs have larger overall impacts on D1 or D2 cells, respectively, supporting a recently proposed hypothesis on the roles of corticostriatal circuits in reinforcement learning.

scholarly journals A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations

2017 ◽  
Vol 37 (41) ◽  
pp. 9977-9998 ◽  
Author(s):  
Andrew Sharott ◽  
Federica Vinciati ◽  
Kouichi C. Nakamura ◽  
Peter J. Magill
Keyword(s):  
Projection Neurons ◽  
Indirect Pathway ◽  
Beta Oscillations ◽  
Striatal Projection Neurons

scholarly journals Chemogenetic restoration of autonomous subthalamic nucleus activity ameliorates Parkinsonian motor dysfunction

2018 ◽  
Author(s):  
Eileen L. McIver ◽  
Hong-Yuan Chu ◽  
Jeremy F. Atherton ◽  
Kathleen E. Cosgrove ◽  
Jyothisri Kondapalli ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Subthalamic Nucleus ◽  
Projection Neuron ◽  
Motor Dysfunction ◽  
Projection Neurons ◽  
List Type ◽  
Oxygen Species ◽  
Striatal Projection Neurons ◽  
Autonomous Activity ◽  
Genetic Mouse Models

Highlightsdecorrelating autonomous STN activity was downregulated in both toxin and genetic models of PDelevation of D2-striatal projection neuron transmission was sufficient for downregulationdownregulation was dependent on activation of STN NMDA receptors and KATP channelschemogenetic restoration of autonomous spiking reduced synaptic patterning of STN neurons and PD motor dysfunctioneToCExcessive synaptic synchronization of STN activity is linked to the symptomatic expression of PD.McIver and colleagues describe the cellular and circuit mechanisms responsible for the loss of decorrelating autonomous STN activity in PD models and demonstrate that chemogenetic rescue of autonomous spiking reduces synaptically patterned STN activity and ameliorates Parkinsonian motor dysfunction.SUMMARYExcessive, synaptically-driven synchronization of subthalamic nucleus (STN) neurons is widely thought to contribute to akinesia, bradykinesia, and rigidity in Parkinson’s disease (PD). Electrophysiological, optogenetic, chemogenetic, genetic, 2-photon imaging, and pharmacological approaches revealed that the autonomous activity of STN neurons, which opposes synaptic synchronization, was downregulated in both toxin and genetic mouse models of PD.Loss of autonomous spiking was due to increased transmission of D2-striatal projection neurons, leading in the STN to elevated activation of NMDA receptors and generation of reactive oxygen species that promoted KATP channel opening.Chemogenetic restoration of autonomous firing in STN neurons reduced synaptic patterning and ameliorated Parkinsonian motor dysfunction, arguing that elevating intrinsic STN activity is an effective therapeutic intervention in PD.

scholarly journals Parallel Movement-suppressing Striatal Output Pathways

2020 ◽  
Author(s):  
Qiaoling Cui ◽  
Xixun Du ◽  
Isaac Y. M. Chang ◽  
Arin Pamukcu ◽  
Varoth Lilascharoen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Body Movement ◽  
Disease Model ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Striatal Projection Neurons ◽  
6 Hydroxydopamine

AbstractThe classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and how they are involved in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting role of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opponent output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes plastic changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.

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.

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