Evaluation of outcome after acute carbon monoxide poisoning by brain CT.

Of 129 patients with carbon monoxide (CO) poisoning, 62(48.0%) had characteristic computed tomographic (CT) findings. The most common finding, seen in 42 patients, was low-density in the cerebral white matter, and the second characteristic feature, seen in 33 patients, was low-density in both globus pallidi. Abnormal CT findings tended to increase in accordance with the duration of unconsciousness during acute CO poisoning, but such findings occurred even when the mental state was clear during acute illness. The prognosis of acute CO poisoning depended on low-density lesions of the cerebral white matter rather than those of the globus pallidus. There also seemed to be a significant correlation between the cerebral white matter changes in the initial CT scan and the development of delayed neurologic sequelae after acute CO poisoning, particularly in middle age or older patients, but no correlation between the CT findings and the clinical outcome of delayed neurologic sequelae.     

Technetium-99m HM-PAO SPECT in patients with delayed neurologic sequelae after carbon monoxide poisoning.

We used single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (99mTc-HM-PAO) in 14 studies on 6 patients with delayed neurologic sequelae from carbon monoxide (CO) poisoning to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed deficits. Among the six initial CT brain scans, two showed low density of both basal ganglia and two showed decreased density of the cerebral white matter. There was no correlation between the clinical outcome and the findings of the follow-up CT brain scans. Of the two SPECTS with 99mTc-HM-PAO performed during acute anoxic insult, one showed focal hypoperfusion which appeared 20 days prior to the onset of delayed neurologic sequelae after CO poisoning. Seven SPECTs in the six patients performing the delayed phase showed diffuse patched patterns of hypoperfusion which improved on follow-up images. There was good correlation between the clinical outcome and the findings of the 99mTc-HM-PAO SPECT. In preliminary conclusion, 9Tc-HM-PAO brain SPECT can be used for predicting or evaluating the outcome of delayed neurologic sequelae after CO poisoning. Cerebral vascular changes may be the possible cause of hypoperfusion in patients with CO poisoning.     

血红素氧合酶系统对一氧化碳中毒后体外培养少突胶质细胞Nogo-A的影响

BACKGROUND: Cerebral white matter demyelination is outstanding in the images of delayed encephalopathy after acute carbon monoxide (CO) poisoning. Since Nogo-A and Nogo-receptor are expressed in onoligodendrocytes and neurons respectively, we infer that Nogo-A system is involved in brain injury after acute CO poisoning and related to delayed encephalopathy after acute CO poisoning. Endogenous CO is a gaseous messenger, which is the metabolic product of hemeoxygenase. There is no report about the CO effect on Nogo-A system till now.OBIECTIVE:To in vitro culture oligodendrocytes using endogenous CO, inhibit the activity of hemeoxygenase system using zinc protoporphyrin-IX (ZnPPIX) and observe the variation of Nogo-A in oligodendrocytes at mRNA and protein levels.METHODS:Rat oligodendrocytes cultured in vitro were divided into control, CO, ZnPPIX groups. Cells in the CO and ZnPPIX groups were treated with 1% CO directly, In the ZnPPIX group, 10 μmol/L ZnPPIX was added into the culture medium before CO treatment. The expressions of Nogo-A mRNA and protein at 6, 24, 48 hours after culture were compared. Differences in the peak levels of Nogo-A mRNA and protein between CO and ZnPPIX groups were detected using RT-PCR and immunohistochemistry respectively.RESULTS:The expression levels of Nogo-A mRNA and protein were significantly higher in the CO group than the control group and reached the peak at 24 hours of culture. Compared with the CO group, oligodendrocytes cultured with ZnPPIX showed higher expressions of Nogo-A mRNA and protein at 24 hours of culture. These findings suggest that except the influence of hypoxia occurring in CO poisoning, exogenous CO increases the expression of Nogo-A in cultured oligodendrocytes in vitro, and the heme oxygenase system can inhibit the expression of Nogo-A mRNA and protein.     

Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease

Maple syrup urine disease (MSUD) is associated with increased branched-chain amino acids (BCAA), their keto acids (BCKA), and acute or chronic encephalopathy. Aim of treatment is to reduce BCAA and BCKA to prevent or minimize brain dysfunction. We investigated 14 juvenile and adult patients with MSUD by means of cerebral magnetic resonance imaging (MRI) and correlated MRI changes to biochemical control measured as median plasma BCAA concentrations over 6-36 months prior to investigation. Abnormalities consisted of an increased signal in the white matter on T2-weighted images which is compatible with a disturbed water content of the white matter and dysmyelination. Areas affected most commonly were mesencephalon, brain stem, thalamus and globus pallidus; supratentorial lesions seem to be restricted to severe cases. No patient with white matter changes had acute neurological/encephalopathic symptoms indicating that the severity of dysmyelination does not correlate to acute neurotoxicity.     

The influence of pallidal deep brain stimulation on striatal dopaminergic metabolism in the rat

Deep brain stimulation of the globus pallidus internus has been recently shown to alleviate parkinsonian symptoms and levodopa-induced dyskinesias. However, its exact mechanisms of action are unclear. Pallidal neurones are connected via various pathways to the dopaminergic nigrostriatal system. In the present study we investigated the hypothesis that deep brain stimulation of the entopeduncular nucleus (corresponds to the human internal pallidum) affects striatal dopaminergic metabolism in naive and 6-hydroxydopamine (6-OHDA) lesioned rats using microdialysis. Our results show that stimulation of the entopeduncular nucleus does not significantly affect striatal dopamine metabolism (of dopamine, 3, 4-dihdroxyphenylacetic acid and homovanillic acid) in naive and 6-OHDA-lesioned animals. They contrast with our previous observations that deep brain stimulation of the subthalamic nucleus increases striatal dopamine metabolism suggesting differential effects of these nuclei on striatal dopamine metabolism.     

Chorea following acute carbon monoxide poisoning

The clinical cases of 6 patients suffering with chorea after acute carbon monoxide (CO) poisoning were reviewed. There were 2 men and 4 women, and the age at onset ranged from 11 to 60 (mean 33.0) years. All the patients except one were associated with mild delayed CO encephalopathy. The latency period between CO poisoning and the onset of chorea was 10 to 30 (mean 21.7) days. The duration of chorea after CO poisoning was 14 to 90 (mean 39.8) days. The brain CT findings were bilateral low- density lesions in the basal ganglia and/or in the white matter of the cerebral cortex, and there was no correlation between the lesion sites on the imagings and the development of chorea. Neuroleptic agents alleviated the chorea and the patients did not relapse after neuroleptic agents were halted.     

Distribution of DARPP-32 in the basal ganglia: an electron microscopic study

Summary DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein, has been studied by light and electron microscopical immunocytochemistry in the rat caudatoputamen, globus pallidus and substantia nigra. In the caudatoputamen, DARPP-32 was present in neurons of the medium-sized spiny type. Immunoreactivity for DARPP-32 was present in dendritic spines, dendrites, perikaryal cytoplasm, most but not all nuclei, axons and a small number of axon terminals. Immunoreactive axon terminals in the caudatoputamen formed symmetrical synapses with immunolabelled dendritic shafts or somata. Neurons having indented nuclei were never immunoreactive. In the globus pallidus and substantia nigra pars reticulata, DARPP-32 was present in myelinated and unmyelinated axons and in axon terminals. The labelled axon terminals in these regions formed symmetrical synaptic contacts on unlabelled dendritic shafts or on unlabelled somata. These data suggest that DARPP-32 is present in striatal neurons of the medium-sized spiny type and that these DARPP-32-immunoreactive neurons form symmetrical synapses on target neurons in the globus pallidus and substantia nigra. The presence of DARPP-32 in these striatal neurons and in their axon terminals suggests that DARPP-32 mediates part of the response of medium-size spiny neurons in the striaturn to dopamine D-l receptor activation.     

Apolipoprotein D in the Niemann-Pick type C disease mouse brain: an ultrastructural immunocytochemical analysis

Enhanced apoD gene expression and abnormally high levels of apoD protein accumulation in the brain have been previously documented as features of the neurodegenerative disorder, Niemann-Pick Type C disease (NP-C). In the present study we have used immunocytochemistry and light and electron microscopy to elucidate the cellular and subcellular distribution of apoD in the Balb/c NIH npc1 ^–/– mouse brain. The normal mouse brain demonstrates low levels of apoD-expressing glia particularly in the cerebellar white matter. In contrast, abundant, strongly apoD-immunolabeled cells were observed in select grey matter nuclei, including the globus pallidus, thalamus, and substantia nigra, and in white matter tracts within the internal capsule and cerebellum of NP-C mouse brain. These brains regions have been previously shown to display the most significant neurodegenerative changes in the NP-C mouse. Ultrastructural analysis revealed dense apoD immunoreactivity on the nuclear envelopes of cells that have the morphological features of oligodendrocyte precursor-like cells and light staining on astrocytes. These results define the cellular and subcellular pattern of expression of apoD in NP-C mouse brain and suggest a possible role for this lipocalin in the pathophysiology of this disorder.     

Diffusion tensor imaging of deep gray matter brain structures: effects of age and iron concentration

Diffusion tensor imaging (DTI) of the brain has become a mainstay in the study of normal aging of white matter, and only recently has attention turned to the use of DTI to examine aging effects in gray matter structures. Of the many changes in the brain that occur with advancing age is increased presence of iron, notable in selective deep gray matter structures. In vivo detection and measurement of iron deposition is possible with magnetic resonance imaging (MRI) because of iron's effect on signal intensity. In the process of a DTI study, a series of diffusion-weighted images (DWI) is collected, and while not normally considered as a major dependent variable in research studies, they are used clinically and they reveal striking conspicuity of the globus pallidus and putamen caused by signal loss in these structures, presumably due to iron accumulation with age. These iron deposits may in turn influence DTI metrics, especially of deep gray matter structures. The combined imaging modality approach has not been previously used in the study of normal aging. The present study used legacy DTI data collected in 10 younger (22-37 years) and 10 older (65-79 years) men and women at 3.0T and fast spin-echo (FSE) data collected at 1.5T and 3.0T to derive an estimate of the field-dependent relaxation rate increase (the "FDRI estimate") in the putamen, caudate nucleus, globus pallidus, thalamus, and a frontal white matter sample comparison region. The effect of age on the diffusion measures in the deep gray matter structures was distinctly different from that reported in white matter. In contrast to lower anisotropy and higher diffusivity typical in white matter of older relative to younger adults observed with DTI, both anisotropy and diffusivity were higher in the older than younger group in the caudate nucleus and putamen; the thalamus showed little effect of age on anisotropy or diffusivity. Signal intensity measured with DWI was lower in the putamen of elderly than young adults, whereas the opposite was observed for the white matter region and thalamus. As a retrospective study based on legacy data, the FDRI estimates were based on FSE sequences, which underestimated the classical FDRI index of brain iron. Nonetheless, the differential effects of age on DTI metrics in subcortical gray matter structures compared with white matter tracts appears to be related, at least in part, to local iron content, which in the elderly of the present study was prominent in the FDRI estimate of the putamen and visibly striking in the diffusion-weighted image of the basal ganglia structures.     

CO中毒后迟发性脑病的临床与脑电图、脑CT分析

目的：探讨CO中毒后迟发性脑病的EEG和脑CT特征及对本病的诊断价值。方法：对63例CO中毒后迟发性脑病的临床与脑电图、脑CT特征进行分析。结果：CO中毒后迟发性脑病的临床主要表现为以痴呆为主的精神障碍，EEG表现为以额叶为主的广泛弥漫性高幅慢波及生理波减弱，阳性率为100％。脑CT主要以皮质下广泛的低密度改变及基底节区局灶性低密度影为特征，部分患CT可正常。结论：EEG和CT能发现CO中毒引起的脑部形态及功能的变化，EEG对DEACMP的敏感性高于CT，EEG在早期诊断DEACMP上优于CT，可作为临床痊愈、判断预后的指标之一。     

NEUROPATHOLOGY OF CREUTZFELDT-JAKOB DISEASE IN JAPAN

Neuropathology of Creutzfeldt-Jakob disease (GJD), particularly of the panencephalopathic type and its additional findings, was described. The panencephalopathic type of CJD was characterized by extensive degeneration of the cerebral white matter which is diffuse in the deep and circumscribed and spongy in the digital white matter. This white matter lesion could not be explained simply as secondary to cortical deterioration. Most cases of the panencephalopathic type disclosed Involvement of anatomically-interrelated systems in various combinations (inferior olivary nucleus-pontine nucleuscerebellar cortex, globus pallidus - subthalamus - substantia nigra, optic tract-lateral geniculate body - optic radiation, and primary thalamic degeneration). These associated findings which could be paralleled as those of combined multisystemic degenerations have been found not only in the panencephalopathic type but also in other subtypes of CJD including Japanese cases of spongiform encephalopathy with multiple kuru plaques. They cannot be considered as coincidental to CJD.     

Neuropathology of Creutzfeldt-Jakob disease in Japan. With special reference to the panencephalopathic type

Neuropathology of Creutzfeldt-Jakob disease (CJD), particularly of the panencephalopathic type and its additional findings, was described. The panencephalopathic type of CJD was characterized by extensive degeneration of the cerebral white matter which is diffuse in the deep and circumscribed and spongy in the digital white matter. This white matter lesion could not be explained simply as secondary to cortical deterioration. Most cases of the panencephalopathic type disclosed involvement of anatomically-interrelated systems in various combinations (inferior olivary nucleus-pontine nucleus-cerebellar cortex, globus pallidus - subthalamus - substantia nigra, optic tract-lateral geniculate body - optic radiation, and primary thalamic degeneration). These associated findings which could be paralleled as those of combined multisystemic degenerations have been found not only in the panencephalopathic type but also in other subtypes of CJD including Japanese cases of spongiform encephalopathy with multiple kuru plaques. They cannot be considered as coincidental to CJD.     

Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network

The subthalamic nucleus-globus pallidus network plays a central role in basal ganglia function and dysfunction. To determine whether the relationship between activity in this network and the principal afferent of the basal ganglia, the cortex, is altered in a model of Parkinson's disease, we recorded unit activity in the subthalamic nucleus-globus pallidus network together with cortical electroencephalogram in control and 6-hydroxydopamine-lesioned rats under urethane anaesthesia. Subthalamic nucleus neurones in control and 6-hydroxydopamine-lesioned animals exhibited low-frequency oscillatory activity, which was tightly correlated with cortical slow-wave activity (approximately 1 Hz). The principal effect of dopamine depletion was that subthalamic nucleus neurones discharged more intensely (233% of control) and globus pallidus neurones developed low-frequency oscillatory firing patterns, without changes in mean firing rate. Ipsilateral cortical ablation largely abolished low-frequency oscillatory activity in the subthalamic nucleus and globus pallidus. These data suggest that abnormal low-frequency oscillatory activity in the subthalamic nucleus-globus pallidus network in the dopamine-depleted state is generated by the inappropriate processing of rhythmic cortical input. A component (15-20%) of the network still oscillated following cortical ablation in 6-hydroxydopamine-lesioned animals, implying that intrinsic properties may also pattern activity when dopamine levels are reduced. The response of the network to global activation was altered by 6-hydroxydopamine lesions. Subthalamic nucleus neurones were excited to a greater extent than in control animals and the majority of globus pallidus neurones were inhibited, in contrast to the excitation elicited in control animals. Inhibitory responses of globus pallidus neurones were abolished by cortical ablation, suggesting that the indirect pathway is augmented abnormally during activation of the dopamine-depleted brain. Taken together, these results demonstrate that both the rate and pattern of activity of subthalamic nucleus and globus pallidus neurones are altered profoundly by chronic dopamine depletion. Furthermore, the relative contribution of rate and pattern to aberrant information coding is intimately related to the state of activation of the cerebral cortex.     

Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging

Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior–posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations.     

Dopaminergic innervation of the rat globus pallidus characterized by microdialysis and immunohistochemistry

The present study examined the dopaminergic innervation of the rat globus pallidus by in vivo microdialysis and immunohistochemistry in more detail. Using tyrosine hydroxylase immunohistochemistry, two classes of dopaminergic fibers were distinguished morphologically in the globus pallidus. Unilateral infusion of 6-hydroxydopamine into the substantia nigra produced a loss of dopaminergic fiber density in the globus pallidus which was correlated with the nigral extent of the lesion. These findings are in line with the notion that a degenerative loss of nigral dopaminergic cell bodies might also affect the dopamine input of extrastriatal structures such as the globus pallidus. Using in vivo microdialysis, we tested whether dopamine measured in the globus pallidus is of neuronal origin. Perfusion of tetrodotoxin induced a strong and transient decrease of pallidal dopamine. The tetrodotoxin-sensitivity of pallidal dopamine demonstrates the functional significance of the nigropallidal dopaminergic innervation.     

Adhesion of Candida albicans to brain tissue of Macaca mulata in an ex vivo assay.

An ex vivo adhesion assay was used to examine adhesion of Candida albicans yeast cells to brain tissue of the primate Macaca mulata. Tissues from frontal lobes and striatum (caudate, putamen, and portions of the globus pallidus) were used in the assay. Yeast cells adhered to gray matter at about six times the level of adhesion to white matter. The fungus was able to bind to different cell types within the cortex, basal ganglia, and white matter. Binding to neurons, small neurons or glia, endothelial cells, and neuropil was observed.     

A sound sleep

Benzodiazepine is a commonly encountered agent of poisoning, which is readily diagnosed by a pertinent history of drug ingestion and the clinical scenario. In the absence of a proper drug history, the diagnosis becomes challenging. Proper clinical assessment, urine assays and imaging play a very important role in reaching the diagnosis. We present a case of acute benzodiazepine poisoning without a history of drug intake. The key pointers toward diagnosis were an unarousable state with obstructive apnea. Magnetic resonance imaging (MRI) of the brain revealed peculiar symmetrical isolated globus pallidus T2 hyperintensity. We believe this to be the first report of isolated bilateral basal ganglia T2-weighted hyperintensity in MRI in the setting of acute benzodiazepine poisoning from India.     

Different effects of dopamine D1 receptor on the firing of globus pallidus neurons in rats

The globus pallidus in rodents, equivalent to the external globus pallidus in primates, plays an important role in movement regulation. Morphological studies have indicated that the globus pallidus receives dopamine innervation from the collaterals of nigrostriatal fibers. To investigate the direct electrophysiological effects of dopamine D(1) receptors in the globus pallidus, in vivo extracellular recordings were performed in the present study. In 25 out of 58 globus pallidus neurons, micro-pressure ejection of 5mM SKF38393 increased the spontaneous firing rate from 9.8 ± 1.9 Hz to 14.3 ± 2.5 Hz. The average increase was 61.5 ± 8.3% (P<0.001). In another 12 out of the 58 globus pallidus neurons, micro-pressure ejection of SKF38393 decreased the spontaneous firing rate from 4.7 ± 1.2 Hz to 2.1 ± 0.6 Hz. The average decrease was 52.1 ± 6.7% (P<0.05). Micro-pressure ejection of SKF38393 did not alter the firing rate significantly in the left 21 globus pallidus neurons. The present findings may provide a rational for further investigations into the potential of pallidal dopamine D(1) receptor in the treatment of Parkinson's disease.     

Relative involvement of globus pallidus and subthalamic nucleus in the regulation of somatodendritic dopamine release in substantia nigra is dopamine-dependent

Previously, we have shown that GABA(A) receptors and glutamate receptors in substantia nigra play distinct roles in the regulation of somatodendritic dopamine release. GABAergic input to substantia nigra was found to be the primary determinant of the level of spontaneous somatodendritic dopamine release. In contrast, acute blockade of dopamine receptors by systemic haloperidol administration produced an increase in somatodendritic dopamine release in substantia nigra that was found to be dependent exclusively upon activation of nigral glutamate receptors. The focus of the present study was to identify anatomical structures that may participate in the differential regulation of somatodendritic dopamine release by GABA and glutamate under these two conditions. To this end, we pharmacologically inhibited the activity of either globus pallidus or subthalamic nucleus using microinfusion of the GABA(A) receptor agonist muscimol. The effects of these manipulations on spontaneous efflux of somatodendritic dopamine and on increases in this measure produced by systemic haloperidol administration were determined in ipsilateral substantia nigra using in vivo microdialysis. As observed previously, administration of haloperidol (0.5 mg/kg, i.p.) significantly increased extracellular dopamine in substantia nigra. Microinfusion of muscimol (400 ng/200 nl) into globus pallidus also produced a significant increase in somatodendritic dopamine efflux. When haloperidol was administered systemically in conjunction with microinfusion of muscimol into globus pallidus, an increase in nigral dopamine efflux was observed that was significantly greater than that which was produced singly by muscimol microinfusion into globus pallidus or by systemic haloperidol administration. The additive nature of the increases in somatodendritic dopamine release produced by these two manipulations indicates that independent neural circuitries may be involved. Inactivation of subthalamic nucleus by microinfusion of muscimol (200 ng/100 nl) had no effect on spontaneous somatodendritic dopamine efflux. Muscimol application into subthalamic nucleus, however, completely abolished the stimulatory effect of systemic haloperidol on dendritic dopamine efflux in substantia nigra.The present data extend our previous findings by demonstrating: 1) an important involvement of globus pallidus efferents in the GABAergic regulation of somatodendritic dopamine efflux in substantia nigra under normal conditions and, 2) an emergent predominant role of subthalamic nucleus efferents in the glutamate-dependent increase in somatodendritic dopamine efflux observed after systemic haloperidol administration. Thus, the relative influence of globus pallidus and subthalamic nucleus in the determination of the level of somatodendritic dopamine release in substantia nigra qualitatively varies as a function of dopamine receptor blockade. These findings are relevant to current models of basal ganglia function under both normal and pathological conditions, e.g. Parkinson's disease.     

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.