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

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.

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Motor thalamus supports striatum-driven reinforcement

eLife ◽

10.7554/elife.34032 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 6

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.

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Neuronal Activity in the Primate Substantia Nigra Pars Reticulata During the Performance of Simple and Memory-Guided Elbow Movements

Journal of Neurophysiology ◽

10.1152/jn.01180.2002 ◽

2004 ◽

Vol 91 (2) ◽

pp. 815-827 ◽

Cited By ~ 31

Author(s):

Thomas Wichmann ◽

Michele Ann Kliem

Keyword(s):

Basal Ganglia ◽

Substantia Nigra ◽

Substantia Nigra Pars Reticulata ◽

Delayed Response ◽

Motor Tasks ◽

Motor Functions ◽

Directional Movement ◽

Anticipatory Activity ◽

Movement Parameters ◽

Response Task

The basal ganglia participate in motor functions and are implicated in the pathophysiology of movement disorders. It has been shown in primates that the activity of many neurons in one of the basal ganglia output nuclei, the internal segment of the globus pallidus, changes with active or passive movements. The involvement of the second major output nucleus, the substantia nigra pars reticulata (SNr), in movement is less well established. In this study, the electrophysiologic activity of SNr neurons was studied in two awake Rhesus monkeys while the animals were examined and while they performed elbow movements in two different motor tasks ( n = 261 cells). Responses to examination were uncommon and subtle. Twenty-one percent of neurons responded to the target step in a step tracking task, mostly with anticipatory responses, although some cells showed directional, movement-related activity. In a delayed-response task, 17% of cells showed anticipatory activity to an instruction cue preceding the target jump, 11% responded directly to the cue, and 11% showed long-lasting postcue activity. Movement-related responses were seen in 21% in this task. Reward responses occurred in 10% of neurons. Responses to more than one event were common. The results demonstrate that few neurons in the SNr respond directly to passive or active movements, but a large proportion shows responses that may be related to memory, attention, or movement preparation. While internal pallidal segment neurons may be preferentially concerned with controlling elemental movement parameters, neurons in the SNr may be more involved in higher motor functions or nonmotor aspects of behavior.

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

eLife ◽

10.7554/elife.42746 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 15

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.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/840247 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 17

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.

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Movement-related coupling of human subthalamic nucleus spikes to cortical gamma

eLife ◽

10.7554/elife.51956 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Petra Fischer ◽

Witold J Lipski ◽

Wolf-Julian Neumann ◽

Robert S Turner ◽

Pascal Fries ◽

...

Keyword(s):

Basal Ganglia ◽

Firing Rate ◽

Subthalamic Nucleus ◽

Information Transfer ◽

Reaction Times ◽

Spike Timing ◽

Neuronal Firing ◽

Gamma Activity ◽

Gamma Phase ◽

Phase Coupling

Cortico-basal ganglia interactions continuously shape the way we move. Ideas about how this circuit works are based largely on models those consider only firing rate as the mechanism of information transfer. A distinct feature of neural activity accompanying movement, however, is increased motor cortical and basal ganglia gamma synchrony. To investigate the relationship between neuronal firing in the basal ganglia and cortical gamma activity during movement, we analysed human ECoG and subthalamic nucleus (STN) unit activity during hand gripping. We found that fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling, indicating a role in motor preparation. Importantly, increased gamma phase coupling occurred independent of changes in mean STN firing rates, and the relative timing of STN spikes was offset by half a gamma cycle for ipsilateral vs. contralateral movements, indicating that relative spike timing is as relevant as firing rate for understanding cortico-basal ganglia information transfer.

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

Journal of Neurophysiology ◽

10.1152/jn.00713.2013 ◽

2014 ◽

Vol 111 (10) ◽

pp. 1949-1959 ◽

Cited By ~ 29

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.

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Dopamine and glutamate control each other's release in the basal ganglia: a microdialysis study of the entopeduncular nucleus and substantia nigra

Neuroscience & Biobehavioral Reviews ◽

10.1016/s0149-7634(96)00032-2 ◽

1997 ◽

Vol 21 (4) ◽

pp. 497-504 ◽

Cited By ~ 24

Author(s):

Christopher S. Biggs ◽

Michael S. Starr

Keyword(s):

Basal Ganglia ◽

Substantia Nigra ◽

Entopeduncular Nucleus ◽

Microdialysis Study

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Cortical Representation of Auditory Space: Information-Bearing Features of Spike Patterns

Journal of Neurophysiology ◽

10.1152/jn.00491.2001 ◽

2002 ◽

Vol 87 (4) ◽

pp. 1749-1762 ◽

Cited By ~ 115

Author(s):

Shigeto Furukawa ◽

John C. Middlebrooks

Keyword(s):

Sound Source ◽

Neuronal Response ◽

Source Location ◽

Spike Timing ◽

Spike Count ◽

Cortical Representation ◽

Auditory Space ◽

Transmitted Information ◽

Related Information ◽

Spike Patterns

Previous studies have demonstrated that the spike patterns of cortical neurons vary systematically as a function of sound-source location such that the response of a single neuron can signal the location of a sound source throughout 360° of azimuth. The present study examined specific features of spike patterns that might transmit information related to sound-source location. Analysis was based on responses of well-isolated single units recorded from cortical area A2 in α-chloralose-anesthetized cats. Stimuli were 80-ms noise bursts presented from loudspeakers in the horizontal plane; source azimuths ranged through 360° in 20° steps. Spike patterns were averaged across samples of eight trials. A competitive artificial neural network (ANN) identified sound-source locations by recognizing spike patterns; the ANN was trained using the learning vector quantization learning rule. The information about stimulus location that was transmitted by spike patterns was computed from joint stimulus-response probability matrices. Spike patterns were manipulated in various ways to isolate particular features. Full-spike patterns, which contained all spike-count information and spike timing with 100-μs precision, transmitted the most stimulus-related information. Transmitted information was sensitive to disruption of spike timing on a scale of more than ∼4 ms and was reduced by an average of ∼35% when spike-timing information was obliterated entirely. In a condition in which all but the first spike in each pattern were eliminated, transmitted information decreased by an average of only ∼11%. In many cases, that condition showed essentially no loss of transmitted information. Three unidimensional features were extracted from spike patterns. Of those features, spike latency transmitted ∼60% more information than that transmitted either by spike count or by a measure of latency dispersion. Information transmission by spike patterns recorded on single trials was substantially reduced compared with the information transmitted by averages of eight trials. In a comparison of averaged and nonaveraged responses, however, the information transmitted by latencies was reduced by only ∼29%, whereas information transmitted by spike counts was reduced by 79%. Spike counts clearly are sensitive to sound-source location and could transmit information about sound-source locations. Nevertheless, the present results demonstrate that the timing of the first poststimulus spike carries a substantial amount, probably the majority, of the location-related information present in spike patterns. The results indicate that any complete model of the cortical representation of auditory space must incorporate the temporal characteristics of neuronal response patterns.

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