Pharmacological blockade of the globus pallidus-induced inhibitory response of subthalamic cells in the rat

Rouzaire-Dubois, B.; Hammond, Constance; Hamon, Brigitte

doi:10.1016/0006-8993(80)90923-3

Cited by 98 publications

(32 citation statements)

References 18 publications

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“…The STN sends excitatory output to the GPe and also receives GABAergic input from the GPe, and thus the GPe may provide feedback inhibition to the STN (Rouzaire- Dubois et al, 1980). It has been shown that the GPe influences the firing rate and discharge pattern as well as the degree of correlated firing of adjacent STN neurons in the rat (Ryan et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor

et al. 2000

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It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization of neuronal firing in the basal ganglia. This study examines the discharge activity of 121 pairs of subthalamic nucleus (STN) neurons in nine PD patients undergoing functional stereotactic mapping. Four patients had a previous pallidotomy. A double microelectrode setup was used to simultaneously record from two neurons separated by distances as small as 250 m. In the six patients who had limb tremor during the recording session (n ϭ 76 pairs), the discharge pattern of 12 pairs of tremor cells (TCs) was found to be coherent at the frequency of the limb tremor. Both in-phase and out-of-phase relationships were observed between TCs. Interestingly, in these six patients, 63/129 single neurons displayed 15-30 Hz oscillations, whereas 36/76 pairs were coherent in this frequency range. Although the oscillatory frequencies were variable between patients, they were highly clustered within a patient. The phase difference between these pairs was found to be close to 0. High-frequency synchronization was observed during periods of limb tremor as well as during intermittent periods with no apparent limb tremor. In contrast, in the three patients without limb tremor during the recording session, only 1/84 neurons had high-frequency oscillatory activity, and no TCs or synchronous high-frequency oscillatory activity was observed (n ϭ 45 pairs). These findings demonstrate that in PD patients with limb tremor, many STN neurons display high-frequency oscillations with a high degree of in-phase synchrony. The results suggest that high-frequency synchronized oscillatory activity may be associated with the pathology that gives rise to tremor in PD patients.

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Section: Discussionmentioning

confidence: 99%

High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor

et al. 2000

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“…Early excitation reflects monosynaptic excitation by cortical afferents (16,55), shortlatency inhibition involves the subthalamo-pallido-subthalamic loop (14,(56)(57)(58)(59)(60), and late-latency excitation results from the delayed disinhibition supplied by indirect corticostriatopallidal inputs to subthalamic neurons (21,61,62).…”

Section: Discussionmentioning

confidence: 99%

Silent plateau potentials, rhythmic bursts, and pacemaker firing: Three patterns of activity that coexist in quadristable subthalamic neurons

Kass

Mintz²

2005

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

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Subthalamic neurons display uncommon intrinsic behaviors that are likely to contribute to the motor and cognitive functions of the basal ganglia and to many of its disorders. Here, we report silent plateau potentials in these cells. These plateau responses start with a transient burst of action potentials that quickly diminish in amplitude because of spike inactivation and current shunt. The resulting interruption of spiking reveals a stable depolarization (up state) that clamps the cell membrane potential near ؊40 mV for several seconds. These plateau potentials coexist in single subthalamic neurons with more familiar patterns of burst and pacemaker firing. Within a narrow range of baseline membrane potentials (؊67 to ؊60 mV), depolarization abruptly switches single cells from bistable to rhythmic bursts or tonic firing modes, thus selecting entirely distinct algorithms for integrating cortical and pallidal synaptic inputs.basal ganglia ͉ bistability ͉ cortex S ubthalamic neurons contribute to the motor (1, 2) and limbic (3, 4) functions of the basal ganglia. Their importance is particularly obvious in Parkinson's disease, in which symptoms improve with high-frequency subthalamic stimulation (5) or subthalamic lesion (6). Thus, there is considerable interest in understanding the synaptic and intrinsic mechanisms that control firing in these cells.At rest, subthalamic neurons display a regular pacemaker activity maintained by sustained (7,8) and resurgent (9) voltagegated Na currents. However, there is little consensus on their firing patterns when they are hyperpolarized.Studies in whole-cell or perforated-patch configurations have reported a quasilinear modulation of cell firing by current injection, excitatory postsynaptic potentials (EPSPs), or inhibitory postsynaptic potentials (IPSPs) (8,(10)(11)(12), with nonlinearities limited to small rebound bursts after IPSPs (13). Consistent with these findings, the in vivo subthalamic responses to cortical stimulation (14-17), their synchronization to cortical slow oscillations (18), and spike-wave discharges (19) are readily explained by the summating contributions of direct cortical inputs and indirect pathways (18,20,21).Studies in whole-cell or cell-attached configurations have revealed more complex bursts of action potentials or spikegenerating plateau potentials that switch to pacemaker firing with membrane depolarization (22-26). These bursts may occur spontaneously (23, 24), generating rhythms strikingly similar to the multisecond-long oscillations reported in subthalamic neurons of locally anesthetized rats (27) and awake monkeys (28).In this study, we investigated the intrinsic behaviors of subthalamic neurons challenged with a wide range of synaptic and current stimuli, during whole-cell, perforated-patch, or cellattached recordings. We found an unexpected homogeneity and complexity in their firing patterns. Independent of the recording conditions, subthalamic neurons display the following four selfsustaining regimes: a resting down state, a quiescent pla...

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“…This excitation results in feedback inhibition (Ryan and Clark, 1992;Nambu et al, 2000;Kolomiets et al, 2001;Kita et al, 2004) and brief synchronization of the STN (Magill et al, 2004). Although in vivo recordings suggest that this inhibition is mediated primarily by GABA A Rs (Rouzaire-Dubois et al, 1980;Kita et al, 1983), the contribution of GABA B Rs has not been examined. Computer simulations suggest that cortically driven elevated firing in GP neurons may lead to GABA B Rmediated hyperpolarization and subsequent rebound burst firing in STN neurons, which is necessary for switching between competing motor programs (Rubchinsky et al, 2003).…”

Section: Functional Implications Of Postsynaptic Gabar Activationmentioning

confidence: 99%

Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABA_Aand GABA_BReceptors

Hallworth¹,

Bevan²

2005

J. Neurosci.

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Reciprocally connected GABAergic neurons of the globus pallidus (GP) and glutamatergic neurons of the subthalamic nucleus (STN) are a putative generator of pathological rhythmic burst firing in Parkinson's disease (PD). Burst firing of STN neurons may be driven by rebound depolarization after barrages of GABA A receptor (GABA A R)-mediated IPSPs arising from pallidal fibers. To determine the conditions under which pallidosubthalamic transmission activates these and other postsynaptic GABARs, a parasagittal mouse brain slice preparation was developed in which pallidosubthalamic connections were preserved. Intact connectivity was first confirmed through the injection of a neuronal tracer into the GP. Voltage-clamp and gramicidin-based perforated-patch current-clamp recordings were then used to study the relative influences of GABA A R-and GABA B R-mediated pallidosubthalamic transmission on STN neurons. Spontaneous phasic, but not tonic, activation of postsynaptic GABA A Rs reduced the frequency and disrupted the rhythmicity of autonomous firing in STN neurons. However, postsynaptic GABA B Rs were only sufficiently activated to impact STN firing when pallidosubthalamic transmission was elevated or pallidal fibers were synchronously activated by electrical stimulation. In a subset of neurons, rebound burst depolarizations followed high-frequency, synchronous stimulation of pallidosubthalamic fibers. Although GABA B Rmediated hyperpolarization was itself sufficient to generate rebound bursts, coincident activation of postsynaptic GABA A Rs produced longer and more intense burst firing. These findings elucidate a novel route through which burst activity can be generated in the STN, and suggest that GABARs on STN neurons could act in a synergistic manner to generate abnormal burst activity in PD.

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Pharmacological blockade of the globus pallidus-induced inhibitory response of subthalamic cells in the rat

Cited by 98 publications

References 18 publications

High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor

High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor

Silent plateau potentials, rhythmic bursts, and pacemaker firing: Three patterns of activity that coexist in quadristable subthalamic neurons

Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABA_Aand GABA_BReceptors

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Pharmacological blockade of the globus pallidus-induced inhibitory response of subthalamic cells in the rat

Cited by 98 publications

References 18 publications

High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor

High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor

Silent plateau potentials, rhythmic bursts, and pacemaker firing: Three patterns of activity that coexist in quadristable subthalamic neurons

Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABAAand GABABReceptors

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Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABA_Aand GABA_BReceptors