Differences in synaptic integration between direct and indirect striatal projection neurons: Role of CaV 3 channels

Synapse ◽  
2018 ◽  
Vol 73 (4) ◽  
pp. e22079 ◽  
Author(s):  
Brisa García-Vilchis ◽  
Paola Suárez ◽  
Miguel Serrano-Reyes ◽  
Mario Arias-García ◽  
Dagoberto Tapia ◽  
...  
Keyword(s):  
Synaptic Integration ◽  
Projection Neurons ◽  
Striatal Projection Neurons

Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat

2015 ◽  
Vol 113 (3) ◽  
pp. 796-807 ◽  
Author(s):  
Ricardo Hernández-Martínez ◽  
José J. Aceves ◽  
Pavel E. Rueda-Orozco ◽  
Teresa Hernández-Flores ◽  
Omar Hernández-González ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Projection Neurons ◽  
Quantal Content ◽  
Short Term ◽  
Paired Pulse ◽  
Short Term Plasticity ◽  
Striatal Projection Neurons ◽  
Muscarinic Cholinergic ◽  
Muscarinic Modulation

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by synapses from striatal projection neurons (SPNs). Because axons from SPNs project to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic in some pallidal neurons. Evidence of muscarinic modulation in any of these elements would suggest that cholinergic afferents from the PPN, or other sources, could modulate the function of the GPe. In this study, we show this evidence using striatopallidal slice preparations: after field stimulation in the striatum, the cholinergic muscarinic receptor agonist muscarine significantly reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses that exhibited short-term synaptic facilitation. This inhibition was associated with significant increases in paired-pulse facilitation, and quantal content was proportional to IPSC amplitude. These actions were blocked by atropine, pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In addition, we found that some pallidal neurons have functional postsynaptic M1 receptors. Moreover, some evoked IPSCs exhibited short-term depression and a different kind of modulation: they were indirectly modulated by muscarine via the activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses presenting distinct forms of short-term plasticity were modulated differently.

scholarly journals KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
M. Belén Pérez-Ramírez ◽  
Antonio Laville ◽  
Dagoberto Tapia ◽  
Mariana Duhne ◽  
Esther Lara-González ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Synaptic Integration ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Kv7 Channels ◽  
Striatal Projection Neurons ◽  
Voltage Dependent ◽  
Cognitive Information ◽  
Firing Properties ◽  
The Impact

Striatal projection neurons (SPNs) process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is theKV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulatingKV7 channels. We found thatKV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

scholarly journals Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Maria-Daniela Cirnaru ◽  
Sicheng Song ◽  
Kizito-Tshitoko Tshilenge ◽  
Chuhyon Corwin ◽  
Justyna Mleczko ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Gene Families ◽  
Projection Neurons ◽  
Open Chromatin ◽  
Striatal Neurons ◽  
Striatal Projection Neurons ◽  
Open Chromatin Region ◽  
Human Ipsc

Many diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating compartmentation and neuronal differentiation are largely unidentified. We performed RNA- and ATAC-seq on sorted striosome and matrix cells at postnatal day 3, using the Nr4a1-EGFP striosome reporter mouse. Focusing on the striosome, we validated the localization and/or role of Irx1, Foxf2, Olig2, and Stat1/2 in the developing striosome and the in vivo enhancer function of a striosome-specific open chromatin region 4.4 Kb downstream of Olig2. These data provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation, including in human iPSC-derived striatal neurons for disease modeling and drug discovery.

scholarly journals Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Marc Deffains ◽  
Liliya Iskhakova ◽  
Shiran Katabi ◽  
Suzanne N Haber ◽  
Zvi Israel ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Field Potential ◽  
Temporal Discounting ◽  
Projection Neurons ◽  
Invasive Treatment ◽  
Cholinergic Interneurons ◽  
Striatal Projection Neurons ◽  
Local Field Potential Lfp ◽  
Spiking Activity

The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders.

The role of Ca2+ channels in the repetitive firing of striatal projection neurons

Neuroreport ◽  
2003 ◽  
Vol 14 (9) ◽  
pp. 1253-1256 ◽  
Author(s):  
Enrique Pérez-Garci ◽  
José Bargas ◽  
Elvira Galarraga
Keyword(s):  
Repetitive Firing ◽  
Projection Neurons ◽  
Striatal Projection Neurons ◽  
Ca2 Channels

Role of striatal projection neurons in the generation of L-DOPA-induced dyskinesia

2016 ◽  
Vol 22 ◽  
pp. e90
Author(s):  
Cristina Alcacer ◽  
Irene Sebastianutto ◽  
Tim Fieblinger ◽  
Johan Jakobsson ◽  
Angela Cenci
Keyword(s):  
Projection Neurons ◽  
Striatal Projection Neurons

scholarly journals Role of striatal ΔFosB in l-Dopa–induced dyskinesias of parkinsonian nonhuman primates

2019 ◽  
Vol 116 (37) ◽  
pp. 18664-18672 ◽  
Author(s):  
Goichi Beck ◽  
Arun Singh ◽  
Jie Zhang ◽  
Lisa F. Potts ◽  
Jong-Min Woo ◽  
...  
Keyword(s):  
Motor Response ◽  
Nonhuman Primates ◽  
Firing Frequency ◽  
Projection Neurons ◽  
Neuronal Responses ◽  
Motor Responses ◽  
Striatal Projection Neurons ◽  
Adaptive Mechanisms

Long-term dopamine (DA) replacement therapy in Parkinson’s disease (PD) leads to the development of abnormal involuntary movements known asl-Dopa–induced dyskinesia (LID). The transcription factor ΔFosB that is highly up-regulated in the striatum following chronicl-Dopa exposure may participate in the mechanisms of altered neuronal responses to DA generating LID. To identify intrinsic effects of elevated ΔFosB onl-Dopa responses, we induced transgenic ΔFosB overexpression in the striatum of parkinsonian nonhuman primates kept naïve ofl-Dopa treatment. Elevated ΔFosB levels led to consistent appearance of LID since the initial acutel-Dopa tests. In line with this motor response, striatal projection neurons (SPNs) responded to DA with changes in firing frequency that reversed at the peak of the motor response, and these unstable SPN activity changes in response to DA are typically associated with the emergence of LID. Transgenic ΔFosB overexpression also induced up-regulation of other molecular markers of LID. These results support an autonomous role of striatal ΔFosB in the adaptive mechanisms altering motor responses to chronic DA replacement in PD.

scholarly journals Transcriptional and epigenetic characterization of early striosomes identifies Foxf2 and Olig2 as factors required for development of striatal compartmentation and neuronal phenotypic differentiation

2020 ◽  
Author(s):  
Maria-Daniela Cirnaru ◽  
Sicheng Song ◽  
Kizito-Tshitoko Tshilenge ◽  
Chuhyon Corwin ◽  
Justyna Mleczko ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Disease Modeling ◽  
Gene Families ◽  
Projection Neurons ◽  
Open Chromatin ◽  
Striatal Projection Neurons ◽  
Human Ipscs ◽  
Open Chromatin Region ◽  
Processing Information

AbstractThe basal ganglia, best known for processing information required for multiple aspects of movement, is also part of a network which regulates reward and cognition. The major output nucleus of the basal ganglia is the striatum, and its functions are dependent on neuronal compartmentation, including striosomes and matrix, which are selectively affected in disease. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), all of which share basic molecular signatures but are subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating terminal neuronal differentiation following migration are largely unidentified. We performed RNA- and ATAC-seq on sorted murine striosome and matrix cells at postnatal day 3. Focusing on the striosomal compartment, we validated the localization and role of transcription factors and their regulator(s), previously not known to be associated with striatal development, including Irx1, Foxf2, Olig2 and Stat1/2. In addition, we validated the enhancer function of a striosome-specific open chromatin region located 15Kb downstream of the Olig2 gene. These data and data bases provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation and thus provide new approaches to establishing MSN subtypes from human iPSCs for disease modeling and drug discovery.

scholarly journals A striatal interneuron circuit for continuous target pursuit

2018 ◽  
Author(s):  
Namsoo Kim ◽  
Haofang E. Li ◽  
Ryan N. Hughes ◽  
Glenn D. R. Watson ◽  
David Gallegos ◽  
...  
Keyword(s):  
The Self ◽  
Target Distance ◽  
Projection Neurons ◽  
Moving Target ◽  
Movement Velocity ◽  
Velocity Transformation ◽  
Striatal Projection Neurons ◽  
Fast Spiking ◽  
Target Pursuit

AbstractMost adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here we show that in the sensorimotor striatum, parvalbumin-positive fast-spiking interneurons (FSIs) can represent the distance between self and target during pursuit behavior, while striatal projection neurons (SPNs), which receive FSI projections, can represent self-velocity. FSIs are shown to regulate velocity-related SPN activity during pursuit, so that movement velocity is continuously modulated by distance to target. Moreover, bidirectional manipulation of FSI activity can selectively disrupt performance by increasing or decreasing the self-target distance. Our results reveal a key role of the FSI-SPN interneuron circuit in pursuit behavior, and elucidate how this circuit implements distance to velocity transformation required for the critical underlying computation.

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