Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Taverna, Stefano; Ilijić, Ema; Surmeier, D. James

doi:10.1523/jneurosci.5493-07.2008

Cited by 364 publications

(504 citation statements)

References 56 publications

(66 reference statements)

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“…This result suggests that iSPN neurons are more sensitive to the transcriptional regulation of VGAT by NO than dSPNs. In line with this idea, we and others have previously found that axon collaterals between SPNs of the two projection systems are not symmetrical because iSPNs profoundly innervate and efficiently inhibit dSPNs (14,20,21). Together with these studies, our experiments suggest that NO signaling regulates motor behavior and action selection by maintaining the normal function of axon collaterals.…”

Section: Dopamine Signaling Regulates Striatal Cgmp and Collateral Vgatsupporting

confidence: 87%

“…3 F and G), suggesting that GABAergic synapses were not being redistributed. GABAergic synapses onto SPNs are derived from one of three sources: fast-spiking (FS) interneurons, neuronal nitric oxide synthase (nNOS)-positive interneurons, and collateral SPN synapses (14,15). FS interneurons make perisomatic synapses that give rise to largeamplitude IPSCs.…”

Section: ) (E)mentioning

confidence: 99%

“…Striatal dopamine depletion is associated with impairments in both striatal NO signaling and GABAergic transmission in axon collaterals of SPNs (14,19). To study the role of dopamine in the regulation of striatal NO signaling and VGAT levels in SPNs, cGMP levels or VGAT labeling was measured in the striata from 6-hydroxydopamine lesioned mice (Fig.…”

Section: Dopamine Signaling Regulates Striatal Cgmp and Collateral Vgatmentioning

confidence: 99%

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Nitric oxide regulates synaptic transmission between spiny projection neurons

Sagi

Heiman

Peterson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance The function of the basal ganglia relies on striatal spiny projecting neurons (SPNs). Axon collaterals of these GABAergic neurons form connections with other SPNs as a means of a feedback inhibition circuit. The mechanisms that regulate neurotransmission at these local synapses remain poorly understood. In this paper, neurotransmission at SPN collaterals is found to be regulated by the gaseous neurotransmitter nitric oxide, which activates a signal-transduction cascade that transcriptionally regulates vesicular GABA transporter specifically at axon collaterals. These findings illustrate a previously unidentified role for nitric oxide in striatal learning and action selection.

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Section: Dopamine Signaling Regulates Striatal Cgmp and Collateral Vgatsupporting

confidence: 87%

Section: ) (E)mentioning

confidence: 99%

Section: Dopamine Signaling Regulates Striatal Cgmp and Collateral Vgatmentioning

confidence: 99%

See 1 more Smart Citation

Nitric oxide regulates synaptic transmission between spiny projection neurons

Sagi

Heiman

Peterson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…41 Second, selectivity of somatotopic neuronal responses to peripheral stimulation is blurred in cortical motor areas 42,43 and basal ganglia nuclei. 44 Third, corticostriatal activity is biased towards activation of striatal neurons in the indirect circuit, 45 which, in association with increased collateral inhibition from medium spiny neurons, 46 leads to globus pallidus pars externa (GPe) inhibition …”

Section: Motor Features Akinesiamentioning

confidence: 99%

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Rodriguez-Oroz

Jahanshahi

Krack

et al. 2009

The Lancet Neurology

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A dopaminergic defi ciency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a defi ciency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine defi ciency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic defi cit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic defi ciency in the early phase of the parkinsonian state and the diff erent circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.

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“…To model the inhibition generated by the striatal inhibitory microcircuits, we modified the channel kinetics of unitary GABAergic synaptic conductances to mimic different inhibitory inputs ( Fig. 3B) (18,19): (i) FS-mediated perisomatic inhibition (FS GABA), (ii) SPN and LTS interneuron-mediated dendritic inhibition with fast kinetics (fast GABA), and (iii) NPY-expressing neurogilaform (NPY-NGF) interneuron-mediated dendritic inhibition with slow kinetics (slow GABA) (26,39,40). We first monitored the membrane potential perturbations (ΔVm) caused by inhibition with different delay timing (Δt Inh ) on plateau potentials (Fig.…”

Section: Model Predicts a Unique Spatiotemporal Window For Cell-type-mentioning

confidence: 99%

Cell-type–specific inhibition of the dendritic plateau potential in striatal spiny projection neurons

Lindroos

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dualcolor uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a celltype-specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg 2+ block. These findings represent a mechanism for controlling spatiotemporal synaptic integration in SPNs.O ne of the principal functions of neurons is to integrate excitatory and inhibitory synaptic inputs and transform subthreshold membrane potential fluctuations into suprathreshold spiking activities. Both theoretical and experimental works have proposed that a single neuron can process inputs as a multilayer computational device in which individual dendritic branches function as a computational unit and can generate dendritic spikes or plateau potentials (1-4). In vivo studies have demonstrated that dendritic plateau potentials evoked by coincident inputs can amplify excitatory signals and enhance the capacity of learning and information storage at a specific branch (5-7). However, a majority of the understanding of dendritic computation is based on studies focusing on pyramidal cells of hippocampal and cortical areas. It is relatively less known whether these conclusions apply to the striatal neurons (8).The striatum, the main input nucleus of the basal ganglia, receives convergent glutamatergic inputs from the cortex and thalamus (9-11). The integration of these functionally distinct inputs is critical for fine movement control and action selection (12, 13). The principal neurons in the striatum-spiny projection neurons (SPNs)-display hyperpolarized membrane potentials (∼−80 mV) at rest, often referred to as the "down-state" (14, 15). It is generally believed that coherent cortical inputs can effectively depolarize SPNs and promote membrane potential transitions from a hyperpolarized down-state to a depolarized "up-state" (∼−55 mV), at which point action potentials can be generated (14-16). To achieve this ∼20-to 30-mV state transition, it has been estimated that a large number (hundreds to thousands) of active inputs would be required (14-17). Interestingly, striatal SPNs are capable of producing long-lasting plateau potentials following activation of spatially clustered and temporally synchronized excit...

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Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Cited by 364 publications

References 56 publications

Nitric oxide regulates synaptic transmission between spiny projection neurons

Nitric oxide regulates synaptic transmission between spiny projection neurons

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Cell-type–specific inhibition of the dendritic plateau potential in striatal spiny projection neurons

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