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.

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 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 during cortical slow‐wave activity and activation

2020 ◽  
Vol 598 (10) ◽  
pp. 1897-1927 ◽  
Author(s):  
Ryan F. Kovaleski ◽  
Joshua W. Callahan ◽  
Marine Chazalon ◽  
David L. Wokosin ◽  
Jérôme Baufreton ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Slow Wave ◽  
Network Dynamics ◽  
Wave Activity ◽  
Slow Wave Activity

scholarly journals Inhibition of Phosphodiesterase 10A Increases the Responsiveness of Striatal Projection Neurons to Cortical Stimulation

2008 ◽  
Vol 328 (3) ◽  
pp. 785-795 ◽  
Author(s):  
Sarah Threlfell ◽  
Stephen Sammut ◽  
Frank S. Menniti ◽  
Christopher J. Schmidt ◽  
Anthony R. West
Keyword(s):  
Cortical Stimulation ◽  
Projection Neurons ◽  
Striatal Projection Neurons ◽  
Phosphodiesterase 10A
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