scholarly journals The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

1994 ◽  
Vol 72 (2) ◽  
pp. 507-520 ◽  
Author(s):  
H. Bergman ◽  
T. Wichmann ◽  
B. Karmon ◽  
M. R. DeLong
Keyword(s):  
Firing Rate ◽  
Subthalamic Nucleus ◽  
Neuronal Activity ◽  
Low Frequency ◽  
Oscillatory Activity ◽  
Autocorrelation Analysis ◽  
Periodic Activity ◽  
Average Firing Rate ◽  
Mptp Treatment ◽  
Highly Correlated

1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) until parkinsonian signs, including akinesia, rigidity, and a prominent 4- to 8-Hz tremor, appeared. The activity of neurons in the subthalamic nucleus (STN) and in the internal segment of the globus pallidus (GPi) was recorded before (STN, n = 220 cells; GPi, n = 175 cells) and after MPTP treatment (STN, n = 326 cells; GPi, n = 154 cells). 2. In STN the spontaneous firing rate was significantly increased from 19 +/- 10 (SD) spikes/s before to 26 +/- 15 spikes/s after MPTP treatment. Division of STN neurons recorded after MPTP treatment into cells with rhythmic bursts of discharge occurring at 4–8 Hz (as defined by autocorrelation analysis) and neurons without 4- to 8-Hz periodic activity revealed an even more prominent increase in the firing rate of the 4- to 8-Hz oscillatory neurons. 3. In GPi overall changes in the average firing rate of cells were inconsistent between different animals and behavioral states. However, the average firing rate of the subpopulation of neurons with 4- to 8-Hz periodic oscillatory activity after treatment with MPTP was significantly increased over that of all neurons before MPTP treatment (from 53 to 76 spikes/s, averaged across monkeys). 4. In the normal state the percentage of neurons with burst discharges (as defined by autocorrelation analysis) was 69% and 78% in STN and GPi, respectively. After MPTP treatment the percentage of cells that discharged in bursts was increased to 79% and 89%, respectively. At the same time the average burst duration decreased (from 121 +/- 98 to 81 +/- 99 ms in STN and from 213 +/- 120 to 146 +/- 134 ms in GPi) with no significant change in the average number of spikes per burst. 5. Periodic oscillatory neuronal activity at low frequency, highly correlated with tremor, was detected in a large number of cells in STN and GPi after MPTP treatment (average oscillation frequency 6.0 and 5.1 Hz, respectively). The autocorrelograms of spike trains of these neurons confirm that the periodic oscillatory activity was very stable. The percentage of cells with 4- to 8-Hz periodic activity significantly increased from 2% to 16% in STN and from 0.6% to 25% in GPi with the MPTP treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Enhanced low-frequency oscillatory activity of the subthalamic nucleus in a patient with dystonia

2012 ◽  
Vol 27 (8) ◽  
pp. 1063-1066 ◽  
Author(s):  
Wolf-Julian Neumann ◽  
Julius Huebl ◽  
Christof Brücke ◽  
Maria Herrojo Ruiz ◽  
Andreas Kupsch ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
Low Frequency ◽  
Oscillatory Activity

scholarly journals Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

2018 ◽  
Author(s):  
Mickaël Degoulet ◽  
Alix Tiran-Cappello ◽  
Christelle Baunez ◽  
Yann Pelloux
Keyword(s):  
Subthalamic Nucleus ◽  
Low Frequency ◽  
Predictive Biomarker ◽  
Progressive Increase ◽  
Oscillatory Activity ◽  
Diagnostic Tools ◽  
Consumption Pattern ◽  
Cocaine Seeking ◽  
Potential Strategy ◽  
Stn Dbs

AbstractCocaine seeking despite a foot-shock contingency is used to model compulsive drug seeking, a core component of drug addiction, in rodents. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is efficient on other addiction criteria models and we show here that 30-Hz STN stimulation reduces pathological cocaine seeking in compulsive-like rats. This confirms STN DBS as a potential strategy to treat addiction. We also observed that only ‘compulsive-like’ rats displayed a progressive increase in STN low frequency oscillations, especially in the alpha/theta band (6-13 Hz), during cocaine escalation. Conversely, applying 8-Hz STN DBS to mimic alpha/theta oscillations in ‘non-compulsive’ animals changed them into ‘compulsive’ ones. We have thus identified a predictive neuronal biomarker of compulsivity. Since one critical challenge in addiction research is to identify vulnerable individuals before they transition to harmful drug consumption pattern, our results could lead to new diagnostic tools and prevention strategies.

scholarly journals Interaction of Indirect and Hyperdirect Pathways on Synchrony and Tremor-Related Oscillation in the Basal Ganglia

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Xia Shi ◽  
Danwen Du ◽  
Yuan Wang
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Low Frequency ◽  
Oscillatory Activity ◽  
Theta Band ◽  
Dynamical Mechanism ◽  
Parkinsonian Tremor ◽  
Cortical Input ◽  
Novel Treatments

Low-frequency oscillatory activity (3-9 Hz) and increased synchrony in the basal ganglia (BG) are recognized to be crucial for Parkinsonian tremor. However, the dynamical mechanism underlying the tremor-related oscillations still remains unknown. In this paper, the roles of the indirect and hyperdirect pathways on synchronization and tremor-related oscillations are considered based on a modified Hodgkin-Huxley model. Firstly, the effects of indirect and hyperdirect pathways are analysed individually, which show that increased striatal activity to the globus pallidus external (GPe) or strong cortical gamma input to the subthalamic nucleus (STN) is sufficient to promote synchrony and tremor-related oscillations in the BG network. Then, the mutual effects of both pathways are analysed by adjusting the related currents simultaneously. Our results suggest that synchrony and tremor-related oscillations would be strengthened if the current of these two paths are in relative imbalance. And the network tends to be less synchronized and less tremulous when the frequency of cortical input is in the theta band. These findings may provide novel treatments in the cortex and striatum to alleviate symptoms of tremor in Parkinson’s disease.

scholarly journals Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement

2017 ◽  
Vol 118 (3) ◽  
pp. 1472-1487 ◽  
Author(s):  
Witold J. Lipski ◽  
Thomas A. Wozny ◽  
Ahmad Alhourani ◽  
Efstathios D. Kondylis ◽  
Robert S. Turner ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Motor Cortex ◽  
Firing Rate ◽  
Subthalamic Nucleus ◽  
Phase Synchronization ◽  
Neuronal Firing ◽  
Oscillatory Activity ◽  
Cortical Oscillations ◽  
Neuronal Firing Rate ◽  
Sensory Cortices

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

Quantitative Analysis of Abducens Neuron Discharge Dynamics During Saccadic and Slow Eye Movements

1999 ◽  
Vol 82 (5) ◽  
pp. 2612-2632 ◽  
Author(s):  
Pierre A. Sylvestre ◽  
Kathleen E. Cullen
Keyword(s):  
Eye Movements ◽  
Firing Rate ◽  
Eye Movement ◽  
Neuronal Activity ◽  
Smooth Pursuit ◽  
Slow Phase ◽  
Vestibular Nystagmus ◽  
Firing Rates ◽  
Rapid Eye Movements ◽  
Eye Velocity

The mechanics of the eyeball and its surrounding tissues, which together form the oculomotor plant, have been shown to be the same for smooth pursuit and saccadic eye movements. Hence it was postulated that similar signals would be carried by motoneurons during slow and rapid eye movements. In the present study, we directly addressed this proposal by determining which eye movement–based models best describe the discharge dynamics of primate abducens neurons during a variety of eye movement behaviors. We first characterized abducens neuron spike trains, as has been classically done, during fixation and sinusoidal smooth pursuit. We then systematically analyzed the discharge dynamics of abducens neurons during and following saccades, during step-ramp pursuit and during high velocity slow-phase vestibular nystagmus. We found that the commonly utilized first-order description of abducens neuron firing rates (FR = b + kE + rE˙, where FR is firing rate, E and E˙ are eye position and velocity, respectively, and b, k, and r are constants) provided an adequate model of neuronal activity during saccades, smooth pursuit, and slow phase vestibular nystagmus. However, the use of a second-order model, which included an exponentially decaying term or “slide” (FR = b + kE + rE˙ + uË − c[Formula: see text]), notably improved our ability to describe neuronal activity when the eye was moving and also enabled us to model abducens neuron discharges during the postsaccadic interval. We also found that, for a given model, a single set of parameters could not be used to describe neuronal firing rates during both slow and rapid eye movements. Specifically, the eye velocity and position coefficients ( r and k in the above models, respectively) consistently decreased as a function of the mean (and peak) eye velocity that was generated. In contrast, the bias ( b, firing rate when looking straight ahead) invariably increased with eye velocity. Although these trends are likely to reflect, in part, nonlinearities that are intrinsic to the extraocular muscles, we propose that these results can also be explained by considering the time-varying resistance to movement that is generated by the antagonist muscle. We conclude that to create realistic and meaningful models of the neural control of horizontal eye movements, it is essential to consider the activation of the antagonist, as well as agonist motoneuron pools.

Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding

1992 ◽  
Vol 68 (5) ◽  
pp. 1859-1866 ◽  
Author(s):  
I. Hamada ◽  
M. R. DeLong
Keyword(s):  
Subthalamic Nucleus ◽  
Neuronal Activity ◽  
Elbow Flexion ◽  
Ibotenic Acid ◽  
Excitatory Input ◽  
Behavioral Task ◽  
Discharge Rates ◽  
Before And After ◽  
The Mean ◽  
Flexion And Extension

1. To gain a better understanding of the pathophysiology of hemiballismus in primates, and to test directly the hypothesis that the subthalamopallidal projection is excitatory, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of monkeys during performance of a motor behavioral task. 2. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The activity of neurons in the external (GPe) and internal (GPi) segments of GP was recorded in two monkeys during task performance before and after STN lesions. The STN was lesioned by the fiber-sparing neurotoxins ibotenic acid and/or kainic acid. 3. After lesioning, the firing rate of neurons in both segments of GP, which was measured during the period of holding before torque application, was significantly decreased in both animals. The mean of discharge rates of GPi neurons decreased (P < 0.001) from 69.8 (n = 169, SD = 21.6) to 47.4 spikes/s (n = 180, SD = 22.6) after lesioning. The mean of discharge rates of GPe neurons decreased from 63.6 spikes/s (n = 218, SD = 25.1) before lesions to 41.0 spikes/s (n = 208, SD = 18.1) after lesioning. 4. These results provide further evidence that STN gives rise to a major excitatory input to both segments of the GP and support the hypothesis that dyskinesias result from decreased GPi output.

Neuronal Activity of the Human Subthalamic Nucleus in the Parkinsonian and Nonparkinsonian State

2008 ◽  
Vol 100 (5) ◽  
pp. 2515-2524 ◽  
Author(s):  
F. Steigerwald ◽  
M. Pötter ◽  
J. Herzog ◽  
M. Pinsker ◽  
F. Kopper ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Essential Tremor ◽  
Subthalamic Nucleus ◽  
Neuronal Activity ◽  
Single Units ◽  
Exact Test ◽  
Spectral Peaks ◽  
Time Changes

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same ( n = 30) or neighboring microelectrodes ( n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1–100 Hz. The distribution of significant oscillations across the theta (1–8 Hz), alpha (8–12 Hz), beta (12–35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test ( P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease.

Sign in / Sign up

Export Citation Format

Share Document