Bidirectional plasticity in striatonigral synapses: A switch to balance direct and indirect basal ganglia pathways

Aceves, José J.; Rueda-Orozco, Pavel E.; Hernández-Martínez, Ricardo; Galarraga, Elvira; Bargas, José

doi:10.1101/lm.023432.111

Cited by 15 publications

(17 citation statements)

References 87 publications

(229 reference statements)

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“…The reduced cortical drive to iMSNs was partially balanced in these cKO mice by an increase in cellular excitability to normalize neuronal output and promote network stability. Synaptic plasticity and modulation, mediated by NMDA-R, is known to explain enduring changes of synaptic weights in microcircuits important for learning and memory storage (Malenka and Bear, 2004;Barbour et al, 2007;Aceves et al, 2011). Consistent with this view, our cKO mice displayed severe phenotypic alterations in behavior.…”

Section: Discussionsupporting

confidence: 82%

Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors

et al. 2016

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The basal ganglia (BG) control action selection, motor programs, habits, and goal-directed learning. The striatum, the principal input structure of BG, is predominantly composed of medium-sized spiny neurons (MSNs). Arising from these spatially intermixed MSNs, two inhibitory outputs form two main efferent pathways, the direct and indirect pathways. Striatonigral MSNs give rise to the activating, direct pathway MSNs and striatopallidal MSNs to the inhibitory, indirect pathway (iMSNs). BG output nuclei integrate information from both pathways to fine-tune motor procedures and to acquire complex habits and skills. Therefore, balanced activity between both pathways is crucial for harmonious functions of the BG. Despite the increase in knowledge concerning the role of glutamate NMDA receptors (NMDA-Rs) in the striatum, understanding of the specific functions of NMDA-R iMSNs is still lacking. For this purpose, we generated a conditional knock-out mouse to address the functions of the NMDA-R in the indirect pathway. At the cellular level, deletion of GluN1 in iMSNs leads to a reduction in the number and strength of the excitatory corticostriatopallidal synapses. The subsequent scaling down in input integration leads to dysfunctional changes in BG output, which is seen as reduced habituation, delay in goaldirected learning, lack of associative behavior, and impairment in action selection or skill learning. The NMDA-R deletion in iMSNs causes a decrease in the synaptic strength of striatopallidal neurons, which in turn might lead to a imbalanced integration between direct and indirect MSN pathways, making mice less sensitive to environmental change. Therefore, their ability to learn and adapt to the environment-based experience was significantly affected.

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Section: Discussionsupporting

confidence: 82%

Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors

et al. 2016

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“…CD-1 mice (25-30 postnatal day) were anesthetized, intracardially perfused, and decapitated, and their brains were obtained. Parasagittal slices (250 -300 m) containing the striatum (Str), external globus pallidus (GPe), subtalamic nucleus (STN), and SNr (de Jesús Aceves et al 2011;Beurrier et al 2006) were obtained with a vibratome in saline with the following (in mM): 124 choline chloride, 2.5 KCl, 1.3 MgCl 2 , 2.4 CaCl 2 , 1.2 NaH 2 PO 4 , 26 NaHCO 3 , and 10 glucose (ϳ4°C, saturated with 95% O 2 -5% CO 2 ). Slices were then incubated for at least 1 h in saline containing the following (in mM): 124 NaCl, 2.5 KCl, 1.3 MgCl 2 , 2 CaCl 2 , 26 NaHCO 3 , 1.2 NaH 2 PO 4 , 10 glucose, 0.2 ascorbic acid, and 0.2 thiourea (pH 7.4, 25-27°C room temperature, saturated with 95% O 2 -5% CO 2 (298 mosmol/l H 2 O).…”

Section: Methodsmentioning

confidence: 99%

“…Its absence induces changes in BG firing patterns that apparently increase with chronicity (MacLeod et al 1990;Rohlfs et al 1997;Sanderson et al 1986;Walters et al 2007), together with an enhancement of indirect pathway activity (Day et al 2006;Graybiel 1996;Murer et al 1997;Parker et al 2016;Weinberger and Dostrovsky 2011), as well as synaptic modifications in both BG pathways (Bellucci et al 2016;Borgkvist et al 2015;Day et al 2006;Maurice et al 2015;Parker et al 2016). Thus unbalance between direct and indirect BG pathways favors SNr burst firing (de Jesús Aceves et al 2011;Ibáñez-Sandoval et al 2007;Lee et al 2013;Walters et al 2007). Therefore, comparing SNr neuron firing during acute DARx and DA depletion may be important in understanding the appearance of pathological firing patterns during DIP.…”

Section: Introductionmentioning

confidence: 99%

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Cáceres-Chávez

Hernández-Martínez

Pérez-Ortega

et al. 2018

Journal of Neurophysiology

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Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism. Dopamine (DA) depletion modifies the firing pattern of neurons in the substantia nigra pars reticulata (SNr), shifting their mostly tonic firing toward irregularity and bursting, traits of pathological firing underlying rigidity and postural instability in Parkinson's disease (PD) patients and animal models of Parkinsonism (PS). Drug-induced Parkinsonism (DIP) represents 20 -40% of clinical cases of PS, becoming a problem for differential diagnosis, and is still not well studied with physiological tools. It may co-occur with tardive dyskinesia. Here we use in vitro slice preparations including the SNr to observe drug-induced pathological firing by using drugs that most likely produce it, DA-receptor antagonists (SCH23390 plus sulpiride), to compare with firing patterns found in DA-depleted tissue. The hypothesis is that SNr firing would be similar under both conditions, a prerequisite to the proposal of a similar preparation to test other DIP-producing drugs. Firing was analyzed with three complementary metrics, showing similarities between DA depletion and acute DAreceptor blockade. Moreover, blockade of either nonselective cationic channels or Ca v 3 T-type calcium channels hyperpolarized the membrane and abolished bursting and irregular firing, silencing SNr neurons in both conditions. Therefore, currents generating firing in control conditions are in part responsible for pathological firing. Haloperidol, a DIP-producing drug, reproduced DA-receptor antagonist firing modifications. Since acute DA-receptor blockade induces SNr neuron firing similar to that found in the 6-hydroxydopamine model of PS, output basal ganglia neurons may play a role in generating DIP. Therefore, this study opens the way to test other DIP-producing drugs.NEW & NOTEWORTHY Dopamine (DA) depletion enhances substantia nigra pars reticulata (SNr) neuron bursting and irregular firing, hallmarks of Parkinsonism. Several drugs, including antipsychotics, antidepressants, and calcium channel antagonists, among others, produce drug-induced Parkinsonism. Here we show the first comparison between SNr neuron firing after DA depletion vs. firing found after acute blockade of DA receptors. It was found that firing in both conditions is similar, implying that pathological SNr neuron firing is also a physiological correlate of drug-induced Parkinsonism.

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“…In rats, entopeduncular/GPi and SNr form the output of the basal ganglia (Deniau & Chevalier, 1984;Bolam & Smith, 1992;Kha et al, 2000;Kolomiets et al, 2003;Aceves et al, 2011). This output contacts ventral motor thalamic nuclei -particularly the ventromedial nucleus (Beckstead et al, 1979;Di Chiara et al, 1979;Herkenham, 1979;Gerfen et al, 1982;Williams & Faull, 1988;Kha et al, 2000Kha et al, , 2001Gulcebi et al, 2012).…”

Section: Basal Ganglia and Striatummentioning

confidence: 99%

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

Sieveritz

García‐Muñoz

Arbuthnott

2018

Eur J of Neuroscience

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The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making.

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Bidirectional plasticity in striatonigral synapses: A switch to balance direct and indirect basal ganglia pathways

Cited by 15 publications

References 87 publications

Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors

Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

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