scholarly journals The Antiparkinsonian and Antidyskinetic Mechanisms ofMucuna pruriensin the MPTP-Treated Nonhuman Primate

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Christopher A. Lieu ◽  
Kala Venkiteswaran ◽  
Timothy P. Gilmour ◽  
Anand N. Rao ◽  
Andrew C. Petticoffer ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Nonhuman Primate ◽  
Chronic Treatment ◽  
Water Extract ◽  
Neuronal Firing ◽  
Mucuna Pruriens ◽  
Drug Induced ◽  
Substantia Nigra Reticulata ◽  
Firing Properties

Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias.Mucuna pruriensendocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects ofMucuna pruriensto determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest thatMucuna pruriensacts through a novel mechanism that is different from that of LD.

Lack of Spike-Count and Spike-Time Correlations in the Substantia Nigra Reticulata Despite Overlap of Neural Responses

2007 ◽  
Vol 98 (4) ◽  
pp. 2232-2243 ◽  
Author(s):  
Alon Nevet ◽  
Genela Morris ◽  
Guy Saban ◽  
David Arkadir ◽  
Hagai Bergman
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Information Transfer ◽  
Spike Timing ◽  
Spike Count ◽  
Unique Event ◽  
Correlated Activity ◽  
Different Types ◽  
Substantia Nigra Reticulata ◽  
Response Task

Previous studies of single neurons in the substantia nigra reticulata (SNr) have shown that many of them respond to similar events. These results, as well as anatomical studies, suggest that SNr neurons share inputs and thus may have correlated activity. Different types of correlation can exist between pairs of neurons. These are traditionally classified as either spike-count (“signal” and “noise”) or spike-timing (spike-to-spike and joint peristimulus time histograms) correlations. These measures of neuronal correlation are partially independent and have different implications. Our purpose was to probe the computational characteristics of the basal ganglia output nuclei through an analysis of these different types of correlation in the SNr. We carried out simultaneous multiple-electrode single-unit recordings in the SNr of two monkeys performing a probabilistic delayed visuomotor response task. A total of 113 neurons (yielding 355 simultaneously recorded pairs) were studied. Most SNr neurons responded to one or more task-related events, with instruction cue (69%) and reward (63%) predominating. Response-match analysis, comparing peristimulus time histograms, revealed a significant overlap between response vectors. However, no measure of average correlation differed significantly from zero. The lack of significant SNr spike-count population correlations appears to be an exceptional phenomenon in the brain, perhaps indicating unique event-related processing by basal ganglia output neurons to achieve better information transfer. The lack of spike-timing correlations suggests that the basal high-frequency discharge of SNr neurons is not driven by the common inputs and is probably intrinsic.

scholarly journals Motor thalamus supports striatum-driven reinforcement

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Arnaud L Lalive ◽  
Anthony D Lien ◽  
Thomas K Roseberry ◽  
Christopher H Donahue ◽  
Anatol C Kreitzer
Keyword(s):  
Synaptic Plasticity ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Projection Neurons ◽  
Direct Pathway ◽  
Substantia Nigra Reticulata ◽  
Motor Thalamus ◽  
Self Stimulation ◽  
Stimulation Of

Reinforcement has long been thought to require striatal synaptic plasticity. Indeed, direct striatal manipulations such as self-stimulation of direct-pathway projection neurons (dMSNs) are sufficient to induce reinforcement within minutes. However, it’s unclear what role, if any, is played by downstream circuitry. Here, we used dMSN self-stimulation in mice as a model for striatum-driven reinforcement and mapped the underlying circuitry across multiple basal ganglia nuclei and output targets. We found that mimicking the effects of dMSN activation on downstream circuitry, through optogenetic suppression of basal ganglia output nucleus substantia nigra reticulata (SNr) or activation of SNr targets in the brainstem or thalamus, was also sufficient to drive rapid reinforcement. Remarkably, silencing motor thalamus—but not other selected targets of SNr—was the only manipulation that reduced dMSN-driven reinforcement. Together, these results point to an unexpected role for basal ganglia output to motor thalamus in striatum-driven reinforcement.

scholarly journals State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Amanda M Willard ◽  
Brian R Isett ◽  
Timothy C Whalen ◽  
Kevin J Mastro ◽  
Chris S Ki ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Neurodegenerative Disorder ◽  
State Transitions ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Dopamine Depletion ◽  
Discrete State ◽  
Substantia Nigra Reticulata ◽  
Diseased State

Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose cardinal motor symptoms are attributed to dysfunction of basal ganglia circuits under conditions of low dopamine. Despite well-established physiological criteria to define basal ganglia dysfunction, correlations between individual parameters and motor symptoms are often weak, challenging their predictive validity and causal contributions to behavior. One limitation is that basal ganglia pathophysiology is studied only at end-stages of depletion, leaving an impoverished understanding of when deficits emerge and how they evolve over the course of depletion. In this study, we use toxin- and neurodegeneration-induced mouse models of dopamine depletion to establish the physiological trajectory by which the substantia nigra reticulata (SNr) transitions from the healthy to the diseased state. We find that physiological progression in the SNr proceeds in discrete state transitions that are highly stereotyped across models and correlate well with the prodromal and symptomatic stages of behavior.

scholarly journals Deep brain stimulation of the subthalamic nucleus reestablishes neuronal information transmission in the 6-OHDA rat model of parkinsonism

2014 ◽  
Vol 111 (10) ◽  
pp. 1949-1959 ◽  
Author(s):  
Alan D. Dorval ◽  
Warren M. Grill
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Information Transmission ◽  
Brain Stimulation ◽  
Rat Model ◽  
Information Transfer ◽  
Firing Pattern ◽  
Signal Propagation ◽  
Neuronal Firing ◽  
Deep Brain

Pathophysiological activity of basal ganglia neurons accompanies the motor symptoms of Parkinson's disease. High-frequency (>90 Hz) deep brain stimulation (DBS) reduces parkinsonian symptoms, but the mechanisms remain unclear. We hypothesize that parkinsonism-associated electrophysiological changes constitute an increase in neuronal firing pattern disorder and a concomitant decrease in information transmission through the ventral basal ganglia, and that effective DBS alleviates symptoms by decreasing neuronal disorder while simultaneously increasing information transfer through the same regions. We tested these hypotheses in the freely behaving, 6-hydroxydopamine-lesioned rat model of hemiparkinsonism. Following the onset of parkinsonism, mean neuronal firing rates were unchanged, despite a significant increase in firing pattern disorder (i.e., neuronal entropy), in both the globus pallidus and substantia nigra pars reticulata. This increase in neuronal entropy was reversed by symptom-alleviating DBS. Whereas increases in signal entropy are most commonly indicative of similar increases in information transmission, directed information through both regions was substantially reduced (>70%) following the onset of parkinsonism. Again, this decrease in information transmission was partially reversed by DBS. Together, these results suggest that the parkinsonian basal ganglia are rife with entropic activity and incapable of functional information transmission. Furthermore, they indicate that symptom-alleviating DBS works by lowering the entropic noise floor, enabling more information-rich signal propagation. In this view, the symptoms of parkinsonism may be more a default mode, normally overridden by healthy basal ganglia information. When that information is abolished by parkinsonian pathophysiology, hypokinetic symptoms emerge.

Striatal dopamine–glutamate interactions reflected in substantia nigra reticulata firing

Neuroreport ◽  
1998 ◽  
Vol 9 (17) ◽  
pp. 3829-3836 ◽  
Author(s):  
Wia Timmerman ◽  
Fiona Westerhof ◽  
Taliet I. C. van der Wal ◽  
Ben H. C. Westerink
Keyword(s):  
Substantia Nigra ◽  
Striatal Dopamine ◽  
Substantia Nigra Reticulata

Role of the Subthalamic Nucleus in Cannabinoid Actions in the Substantia Nigra of the Rat

1997 ◽  
Vol 77 (3) ◽  
pp. 1635-1638 ◽  
Author(s):  
M. Clara Sañudo-Peña ◽  
J. Michael Walker
Keyword(s):  
Substantia Nigra ◽  
Subthalamic Nucleus ◽  
Cannabinoid Receptors ◽  
Excitatory Input ◽  
Physiological Regulation ◽  
Cannabinoid Antagonist ◽  
Substantia Nigra Reticulata ◽  
Cannabinoid Agonist ◽  
Stimulation Of

Sañudo-Peña, M. Clara and J. Michael Walker. Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat. J. Neurophysiol. 77: 1635–1638, 1997. The effect of cannabinoids on the excitatory input to the substantia nigra reticulata (SNr) from the subthalamic nucleus was explored. For this purpose a knife cut was performed rostral to the subthalamic nucleus to isolate the subthalamic nucleus and the SNr from the striatum, a major source of cannabinoid receptors to the SNr. The data showed that the cannabinoid agonist WIN55,212-2 blocked the increase in the firing rate of SNr neurons induced by stimulation of the subthalamic nucleus with bicuculline. Furthermore, the cannabinoid antagonist SR141716A antagonized the effect of the cannabinoid agonist. This study showed that cannabinoids regulate not only the striatonigral pathway, as previously reported, but also the subthalamonigral pathway. The opposite influences of these two inputs to the SNr, inhibitory and excitatory respectively, suggest that endogenous cannabinoids play a major role in the physiological regulation of the SNr.

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