Pallidal Activity Research Articles

Serotonin Activates Presynaptic and Postsynaptic Receptors in Rat Globus Pallidus

Although recent histological, behavioral, and clinical studies suggest that serotonin (5-HT) plays significant roles in the control of pallidal activity, only little is known about the physiological action of 5-HT in the pallidum. Our recent unit recording study in monkeys suggested that 5-HT provides both presynaptic and postsynaptic modulations of pallidal neurons. The present study using rat brain slice preparations further explored these presynaptic and postsynaptic actions of 5-HT. Bath application of 5-HT or the 5-HT(1A/1B/1D/5/7) receptor (R) agonist 5-carboxamidotryptamine maleate (5-CT) depolarized some and hyperpolarized other pallidal neurons. Pretreatments of slices with blockers of the hyperpolarization-cyclic nucleotide-activated current or with the 5-HT(2/7)R-selective antagonist mesulergine occluded 5-CT-induced depolarization. The 5-HT(1A)R-selective blocker N-[2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohex-anecarboxamide maleate occluded the 5-CT-induced hyperpolarization. These results suggested involvement of 5-HT(7)R and 5-HT(1A)R in the postsynaptic depolarization and hyperpolarization, respectively. 5-CT presynaptically suppressed both internal capsule stimulation-induced excitatory postsynaptic currents (EPSCs) and striatal stimulation-induced inhibitory postsynaptic currents (IPSCs). The potencies of 5-CT on the presynaptic effects were 20- to 25-fold higher than on postsynaptic effects, suggesting that 5-HT mainly modulates presynaptic sites in the globus pallidus. Experiments with several antagonists suggested involvement of 5-HT(1B/D)R in the presynaptic suppression of EPSCs. However, the receptor type involved in the presynaptic suppression of IPSCs was inconclusive. The present results provided evidence that 5-HT exerts significant control over the synaptic inputs and the autonomous activity of pallidal neurons.

Is the synchronization between pallidal and muscle activity in primary dystonia due to peripheral afferance or a motor drive?

The pathophysiological mechanisms of primary dystonia have largely remained obscure. Yet there is one undeniable observation: lesioning or high-frequency stimulation of the internal segment of the globus pallidus (GP) ameliorates dystonic symptoms. The latter observation implicates abnormal pallidal activity in the genesis of primary dystonia. Recently, excessive oscillatory pallidal activity in the 3-10 Hz frequency range, synchronized with dystonic EMG, has been related to the occurrence of involuntary muscle activity in these patients. However, it is unclear whether this pathological synchronization is driven by GP, caused by re-afference from dystonic muscle, or due to a combination of these two processes. Here we used the Directed Transfer Function as a spectral measure to identify the degree and direction of coupling across time between GP and muscle in seven patients with primary dystonia. We show that pallidal local field potential activity <or= 10 Hz is coherent with dystonic movements, and that although the coupling between GP and activity in the sternocleidomastoid muscle is bidirectional, the drive from GP to muscle significantly outweighs that from muscle to GP. In addition, the net GP drive to muscle is not stable but fluctuates across time, in keeping with the dynamic nature of dystonic muscle activity.

Motor cortical control of internal pallidal activity through glutamatergic and GABAergic inputs in awake monkeys

The internal segment of the globus pallidus (GPi) receives motor-related cortical signals mainly through the striatum, the external segment of the globus pallidus (GPe) and the subthalamic nucleus (STN). The GPi sends its outputs outside the basal ganglia and plays a key role in motor control. Extracellular unit recordings were performed in awake monkeys to explore how glutamatergic STN inputs and GABAergic striatal and GPe inputs control spontaneous activity and how these inputs contribute to motor cortex stimulation-induced responses of GPi neurons. The typical responses of GPi neurons to cortical stimulation consisted of an early excitation, an inhibition and a late excitation. Local applications of the NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid and/or the AMPA/kainate receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide in the vicinity of recorded GPi neurons reduced the firing rate, and abolished or attenuated both early and late excitations following cortical stimulation. Local application of the GABA(A) receptor antagonist gabazine increased the firing rate, induced oscillatory firings and diminished the cortically induced inhibition. Muscimol or gabazine injection into the STN or GPe also altered the firing rate, and attenuated the late excitation of GPi neurons. The gabazine injection into the STN occasionally induced dyskinesia with significantly decreased GPi activity. These data suggest that the early and late excitations are glutamatergic and induced by the cortico-STN-GPi and cortico-striato-GPe-STN-GPi pathways, respectively. The inhibition is GABAergic and induced by the cortico-striato-GPi pathway. In addition, these inputs are the main factors governing the spontaneous activity of GPi neurons.

Pallidal Neuron Activity Increases during Sensory Relay through Thalamus in a Songbird Circuit Essential for Learning

Disinhibition of the thalamus remains the primary model of information transfer between the basal ganglia and the cortex. Yet in apparent conflict with this model, the globus pallidus, a GABAergic basal ganglia output structure, often exhibits marked increases in firing rate during movement. To investigate the translation of pallidal activity and its relay through the thalamus, we explored a basal ganglia-thalamic pathway essential for song learning in songbirds. We found that single units in the thalamic nucleus DLM of urethane-anesthetized adult male zebra finches responded selectively to playback of the bird's own song, like neurons in its upstream and downstream nuclei. Because the pallidal input to these neurons forms giant calyx-like synapses, we were able to record extracellular signals from these presynaptic terminals as well. Pallidal units were distinctly excited by song playback, suggesting an increase in GABAergic transmission in the thalamus during sensory processing. However, this overall increased firing rate was phasic, punctuated by rapid decelerations in firing rate. In several cases, we were able to record presynaptic and postsynaptic units simultaneously. Correlating the presynaptic and postsynaptic activity, we found that disinhibition of thalamus may entail pallidal firing rate decelerations rather than simple long pauses in spontaneous activity, as has long been assumed.

Changes in cortical and pallidal oscillatory activity during the execution of a sensory trick in patients with cervical dystonia

We examined the effects of a sensory trick (SeT) on cortical EEG and globus pallidus (GP) local field potentials in four cervical dystonia patients, two of whom had an effective SeT and two who did not. The application of an effective SeT was associated with bilateral desynchronization in the 6–8 Hz and β bands in the GP and sensorimotor cortical regions. In contrast, mimicking an SeT led to a worsening of dystonia, which was associated with desynchronization of the β band and synchronization in the 4–6 Hz range. These preliminary findings suggest a role for 4–8 Hz frequency synchronization in the pathophysiology of dystonia.

Internal Pallidal Neuronal Activity During Mild Drug-Related Dyskinesias in Parkinson's Disease: Decreased Firing Rates and Altered Firing Patterns

The neuronal basis of hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to dyskinesias induced by low doses of apomorphine in patients with advanced Parkinson's disease (PD). During pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of apomorphine at doses just adequate to induce dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with dyskinesias. Among the three neurons in which the onset of on occurred before that of dyskinesias, the firing rate did not change at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias during on with dyskinesias often fluctuated between transient periods with dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with dyskinesias. These results suggest that mild dyskinesias resulting from low doses of apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.

Glutamatergic and GABAergic modulation of monkey pallidal neuron activity in relation to motor task

Glutamatergic and GABAergic modulation of monkey pallidal neuron activity in relation to motor task

Dopamine Replacement Therapy Does Not Restore the Full Spectrum of Normal Pallidal Activity in the 1-Methyl-4-Phenyl-1,2,3,6-Tetra-Hydropyridine Primate Model of Parkinsonism

Current physiological studies emphasize the role of neuronal oscillations and synchronization in the pathophysiology of Parkinson's disease; however, little is known about their specific roles in the neuronal substrate of dopamine replacement therapy (DRT). We investigated oscillatory activity and correlations throughout the different states of levodopa-naive parkinsonism as well as "Off-On" and dyskinetic states of DRT in the external globus pallidum (GPe) of tremulous (vervet) and rigid-akinetic (macaque) monkeys and in the internal globus pallidum (GPi) of the vervet monkey. We found that, although oscillatory activity of cells and interneuronal correlation in both pallidal segments increases after induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and decreases in response to DRT, important differences exist between the two pallidal segments. In the GPi, the fraction of oscillatory cells and relative power of oscillations were significantly higher than in the GPe, and the dominant frequency was within the range of 7.5-13.5 Hz compared with a range of 4.5-7.5 Hz within the GPe. The interneuronal correlations were mostly oscillatory in the GPi, whereas at least half are non-oscillatory in the GPe. We demonstrate that the tremor characteristics after exposure to DRT do not resemble those of the normal or the levodopa-naive state. Moreover, although DRT reverses the MPTP-induced neuronal changes (rate, pattern, and pairwise correlations), the balance between GPe and GPi fails to restore. We therefore suggest that this imbalance reflects additional abnormal organization of the basal ganglia networks in response to dopamine replacement and may constitute the physiological substrate of the limitations and side effects of chronic DRT.

Oscillatory pallidal local field potential activity correlates with involuntary EMG in dystonia

The pathophysiology of dystonia is unclear. The authors recorded local field potentials (LFPs) from deep brain stimulation electrodes implanted in the pallidum of 13 dystonic patients. LFP power correlated with the level of dystonic EMG in the sternocleidomastoid, with maximal positive correlations at the lower contacts of pallidal electrodes. The data suggest that the neuronal synchronization indexed by LFP oscillations in the globus pallidus may be mechanistically linked to dystonic EMG activity.

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8–16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.

Down‐regulation of metabotropic glutamate receptor 1α in globus pallidus and substantia nigra of parkinsonian monkeys

Enhanced glutamatergic neurotransmission via the subthalamopallidal or subthalamonigral projection seems crucial for developing parkinsonian motor signs. In the present study, the possible changes in the expression of metabotropic glutamate receptors (mGluRs) were examined in the basal ganglia of a primate model for Parkinson's disease. When the patterns of immunohistochemical localization of mGluRs in monkeys administered systemically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were analysed in comparison with normal controls, we found that expression of mGluR1alpha, but not of other subtypes, was significantly reduced in the internal and external segments of the globus pallidus and the substantia nigra pars reticulata. To elucidate the functional role of mGluR1 in the control of pallidal neuron activity, extracellular unit recordings combined with intrapallidal microinjections of mGluR1-related agents were then performed in normal and parkinsonian monkeys. In normal awake conditions, the spontaneous firing rates of neurons in the pallidal complex were increased by DHPG, a selective agonist of group I mGluRs, whereas they were decreased by AIDA, a selective antagonist of group I mGluRs, or LY367385, a selective antagonist of mGluR1. These electrophysiological data strongly indicate that the excitatory mechanism of pallidal neurons by glutamate is mediated at least partly through mGluR1. The effects of the mGluR1-related agents on neuronal firing in the internal pallidal segment became rather obscure after MPTP treatment. Our results suggest that the specific down-regulation of pallidal and nigral mGluR1alpha in the parkinsonian state may exert a compensatory action to reverse the overactivity of the subthalamic nucleus-derived glutamatergic input that is generated in the disease.

Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch–Nyhan syndrome

Objective. – Lesch–Nyhan syndrome is a rare and debilitating condition characterized by dystonia and self-mutilating behavior. In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS). Methods. – Microrecordings were performed on 162 neurons along four tracks aimed at the right and left anterior (limbic) and posterior (motor) globus pallidus internus (GPI). Results. – Regardless of the anesthetic agent used (propofol or sevoflurane), both patients showed similar neurons firing rates in the four regions studied, namely the limbic and motor portions of the globus pallidus externus (GPE) or GPI. In both patients, firing rates were similar in the GPE (12.2 ± 1.8 Hz, N = 38) and GPI (13.2 ± 1.0 Hz, N = 83) portions of the limbic track, while the motor GPE fired at a higher frequency (23.8 ± 2.7 Hz, N = 18) than the motor GPI (12.5 ± 1.4 Hz, N = 23). Conclusions. – These results demonstrate that light propofol or sevoflurane anesthesia influences pallidal activity in a similar way. Electrophysiological recordings suggest that Lesch–Nyhan syndrome might be characterized by analogous firing frequencies in the limbic GPE and GPI while motor GPE would tend to fire at higher rate than the motor GPI. It is therefore tempting to suggest that the symptoms that are observed in Lesch–Nyhan syndrome might result from motor GPI inhibition. Significance. – This observation may confirm the Albin and Delong's model of the basal nuclei in hypokinetic and hyperkinetic disorders.

Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease

Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = −0.65, P < 0.001 and r = −0.33, P < 0.001 for activities over 13–30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.

GABAergic Modulation of the Activity of Globus Pallidus Neurons in Primates: In Vivo Analysis of the Functions of GABA Receptors and GABA Transporters

Neurons in the external and internal segment of the globus pallidus (GPe and GPi, respectively) receive substantial GABAergic inputs from the striatum and through axon collaterals of neighboring pallidal neurons. The effects of GABA on pallidal activity depend on the synaptic localization of GABA receptors and the distribution and activity of GABA transporters (GATs). To explore the contribution of GABA receptors and transporters to pallidal function, we recorded the activity of single neurons in GPe or GPi before, during, and after local microinjections of GABAergic compounds in awake rhesus monkeys. Activation of GABA(A) or GABA(B) receptors with muscimol or baclofen, respectively, inhibited pallidal activity. These effects were reversed by concomitant infusion of the respective GABA receptor antagonists, gabazine and CGP-55845. Given alone, the antagonists were without consistent effect. Application of the selective GAT-1 inhibitor, SKF-89976A, and the semiselective GAT-3 blocker, SNAP-5114, decreased pallidal activity. Both GAT inhibitors increased GABA levels in the pallidum, as measured by microdialysis. Electron microscopic observations revealed that these transporters are located on glial processes and unmyelinated axonal segments, but rarely on terminals. Our results indicate that activation of GABA(A) and GABA(B) receptors inhibits neuronal activity in both segments of the pallidum. GAT-1 and GAT-3 are involved in the modulation of endogenous GABA levels and may be important in regulating the extrasynaptic levels of GABA. Together with previous evidence that a considerable proportion of pallidal GABA receptors are located outside the synaptic cleft, our experiments strongly support the importance of extrasynaptic GABAergic transmission in the primate pallidum.

Context-Dependent Modulation of Movement-Related Discharge in the Primate Globus Pallidus

A selective contribution of the basal ganglia (BG) to memory-contingent motor control has long been hypothesized. The importance of memory context remains an open question, however, for the BG skeletomotor circuit. To investigate this question, we studied the perimovement discharge of a carefully selected group of 74 "arm-related" pallidal cells in two rhesus monkeys. The animals performed three tasks designed to dissociate multiple independent aspects of memory-contingent reaching while controlling movement kinematics. The activity of most neurons (88%) was influenced strongly by the memory demands of a task (remembering "where" or "when" to move), but the population as a whole showed no systematic preference for memory- or sensory-contingent conditions. The effects of memory context were primarily additive with those of movement kinematics (particularly movement direction). Considered separately, decreases and increases in firing had very different context preferences: decreases were nearly always larger for sensory-triggered movements, whereas increases were enhanced most often under memory-contingent conditions (i.e., self-initiated or self-guided movements). A similar pattern of preferences was found for both pallidal segments. The distinct context-specific enhancements of decreases and increases could not be explained as simple sensory responses or as interactions with preparatory or anticipatory processes present before movement initiation. Rather, they appear related to movement execution under specific contexts. Our results lead to the conclusion that movement facilitatory decreases in internal pallidal (GPi) activity are primarily greater under sensory-triggered conditions. GPi increases and their suppressive effects, perhaps on competing activity in pallidal-recipient centers, have increased prevalence under memory-contingent conditions.

Independent Coding of Movement Direction and Reward Prediction by Single Pallidal Neurons

Associating action with its reward value is a basic ability needed by adaptive organisms and requires the convergence of limbic, motor, and associative information. To chart the basal ganglia (BG) involvement in this association, we recorded the activity of 61 well isolated neurons in the external segment of the globus pallidus (GPe) of two monkeys performing a probabilistic visuomotor task. Our results indicate that most (96%) neurons responded to multiple phases of the task. The activity of many (34%) pallidal neurons was modulated solely by direction of movement, and the activity of only a few (3%) pallidal neurons was modulated exclusively by reward prediction. However, the activity of a large number (41%) of single pallidal neurons was comodulated by both expected trial outcome and direction of arm movement. The information carried by the neuronal activity of single pallidal neurons dynamically changed as the trial progressed. The activity was predominantly modulated by both outcome prediction and future movement direction at the beginning of trials and became modulated mainly by movement-direction toward the end of trials. GPe neurons can either increase or decrease their discharge rate in response to predicted future reward. The effects of movement-direction and reward probability on neural activity are linearly summed and thus reflect two independent modulations of pallidal activity. We propose that GPe neurons are uniquely suited for independent processing of a multitude of parameters. This is enabled by the funnel-structure characteristic of the BG architecture, as well as by the anatomical and physiological properties of GPe neurons.

Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson's disease

The pattern of neuronal discharge within the basal ganglia is disturbed in Parkinson's disease (PD). In particular, there is a tendency for neuronal elements to synchronise at around 20 Hz in the absence of dopaminergic treatment, whereas this activity can be replaced by spontaneous synchronisation at much higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21 (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at similar frequencies in the globus pallidus interna, the major output structure of the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the subthalamic area at similar high frequencies reverses parkinsonism and forms the basis of therapeutic deep brain stimulation in PD. The results point to a possible common mechanism by which both dopaminergic treatment associated synchronisation of subthalamic activity at very high frequency and synchronisation imposed by therapeutic stimulation of the subthalamic area inhibit an abnormal and potentially deleterious synchronisation of basal ganglia output at around 20 Hz. If this activity is unchecked by synchronisation at higher frequency, then pathological 20-Hz oscillations may cascade through the basal ganglia, increasing at subsequent levels of processing.

Severity of negative symptoms in Schizophrenia correlated to Hyperactivity of the left globus pallidus and the right claustrum. A PET Study.

SummarySchizophrenia has been characterized as a complex disease, in which various cerebral regions may be affected. The purpose of this study was to compare the cerebral regions that are involved in mild and severe negative symptoms, and to determine whether the degree of severity can be related to specific dysfunctional areas of the brain.The PANS Scale was used to form two groups of patients with prevalence of negative symptoms: Mildly Affected (MA), and Severely Affected (SA). Brain PETs were obtained in resting conditions, and SPM (Statistical Parametric Mapping) was used to perform statistical comparisons.The MA-group showed increased activity in: posterior cingulate gyrus, middle frontal gyrus, precentral gyrus, middle occipital gyrus, cuneus and post-central gyrus; decreased activity in inferior frontal gyrus, orbitofrontal and fusiform gyrus.The SA-group showed increased activity in: globus pallidus, insular cortex, cuneus, claustrum, post-central gyrus and pre-central gyrus; decreased acti-vity in fusiform gyrus and superior temporal gyri. These results show correlation of negative symptomatology with abnormalities in the cortico-striato-pallido-thalamic neural circuit. Severity of negative symptoms is clearly correlated to abnormal left external pallidal activation, evidencing the relevance of this nucleus for cognitive, planning and social capabilities. Specific therapeutic strategies might be derived from pallidal neurotransmitter systems studies.

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

The firing patterns of dopaminergic neurons in vivo are strongly modulated by afferent input. The principal GABAergic inputs to the dopaminergic neurons of the substantia nigra originate from neurons of the neostriatum, globus pallidus and substantia nigra pars reticulata. It has previously been shown that the firing pattern of nigral dopaminergic neurons can be manipulated by pharmacologically induced excitation or inhibition of the globus pallidus with relatively little effect on firing rate. We used this technique to explore the relation between the firing pattern of dopaminergic neurons and extracellular dopamine levels in the neostriatum in vivo. Specifically, we tested whether an increase in burst firing in dopaminergic neurons produced by increased pallidal activity led to increased extracellular dopamine levels in the neostriatum. Single unit extracellular recording combined with simultaneous microdialysis was used to measure the firing rates and patterns of dopaminergic neurons and extracellular striatal dopamine levels, respectively, during bicuculline-induced excitation of the globus pallidus. Pallidal excitation resulted in a marked increase in burst firing in dopaminergic neurons along with only a slight increase in firing rate, but produced a significant elevation (approximately 45%) in neostriatal dopamine levels. These data suggest that afferent-induced burst firing in dopaminergic neurons leads to an increase in extracellular dopamine levels in the neostriatum when compared with less bursty patterns with similar overall firing rates.

Functional Correlations between Neighboring Neurons in the Primate Globus Pallidus Are Weak or Nonexistent

The anatomical structure of the basal ganglia displays topographical organization and massive funneling of neuronal projections toward the globus pallidus as well as an axonal collateral system within this nucleus. This structure suggests the formation of correlations between the spiking activities of pallidal cells. Nevertheless, previous studies of remote neurons in the pallidum have reported uncorrelated spiking activity. These correlation results may be challenged, because remote pallidal neurons may be located in different pallidal territories. To further test the independence of pallidal activity, we studied the spiking activity of neighboring pairs recorded by the same electrodes. A narrow peak dominated the correlations of all pairs of neurons recorded on the same electrode. This type of peak is classically interpreted as a sign of strong common input. However, recent mathematical analysis shows that such peaks may derive from a technical inability to detect overlapping spikes by spike-sorting techniques. A long-term shallow trough in the correlation of neighboring neurons may also result from the same effect, which we have termed the "shadowing effect." A comparison of the expected shadowing effect with the actual correlations suggests that no real correlations exist between 93.9% of neighboring pallidal pairs. The remaining 6.1% of the pairs display symmetric long-term positive correlations centered on time 0. Thus, functional interactions between neighboring pallidal neurons do not display any significant differences from the interactions between physically remote neurons in this brain area. Moreover, the combination of anatomical data and current physiological results suggests an active decorrelating process performed in the basal ganglia.