The functional anatomy of disorders of the basal ganglia

Albin, Roger L.; Young, Anne B.; Penney, John B.

doi:10.1016/0166-2236(95)80020-3

Cited by 529 publications

(585 citation statements)

References 10 publications

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“…These parameters correspond to the level of striatal input to GPe and interpallidal inhibition, respectively. Note that experimental results show an increase in striatal inhibition to GPe (e.g., Albin et al, 1989) and a decrease in intrapallidal inhibition (Stanford et al, 1999;Ogura et al, 2000) in parkinsonian conditions. By a "normal state", we mean that the parameters are chosen so that the STN/GPe network produces the irregular pattern shown in left panels of Fig.…”

Section: Normal and Parkinsonian Statesmentioning

confidence: 84%

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

2004

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Abstract. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) has recently been recognized as an important form of intervention for alleviating motor symptoms associated with Parkinson's disease, but the mechanism underlying its effectiveness remains unknown. Using a computational model, this paper considers the hypothesis that DBS works by replacing pathologically rhythmic basal ganglia output with tonic, high frequency firing. In our simulations of parkinsonian conditions, rhythmic inhibition from GPi to the thalamus compromises the ability of thalamocortical relay (TC) cells to respond to depolarizing inputs, such as sensorimotor signals. High frequency stimulation of STN regularizes GPi firing, and this restores TC responsiveness, despite the increased frequency and amplitude of GPi inhibition to thalamus that result. We provide a mathematical phase plane analysis of the mechanisms that determine TC relay capabilities in normal, parkinsonian, and DBS states in a reduced model. This analysis highlights the differences in deinactivation of the low-threshold calcium T -current that we observe in TC cells in these different conditions. Alternative scenarios involving convergence of thalamic signals in the cortex are also discussed, and predictions associated with these results, including the occurrence of rhythmic rebound bursts in certain TC cells in parkinsonian states and their drastic reduction by DBS, are stated. These results demonstrate how DBS could work by increasing firing rates of target cells, rather than shutting them down.

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Section: Normal and Parkinsonian Statesmentioning

confidence: 84%

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

2004

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“…STN is in a central position in the motor, associative and limbic circuit within the cortico-basal ganglia-thalamocortical loops (Albin et al, 1989;Alexander et al, 1986). In the limbic circuit, the NAC, the VP (ventral pallidum), and the prefrontal cortex are known to be involved in ethanol reinforcement (Bassareo et al, 2003;Doyon et al, 2003;Samson and Czachowski, 2003).…”

Section: Discussionmentioning

confidence: 99%

Alcohol Preference Influences the Subthalamic Nucleus Control on Motivation for Alcohol in Rats

Lardeux

Baunez

2007

Neuropsychopharmacol

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In addition to its role in motor and attentional processes, the subthalamic nucleus (STN) has also been recently demonstrated to be involved in motivational function. Indeed, bilateral STN lesions modulate differentially the motivation for natural rewards and drugs of abuse, increasing motivation for food and decreasing motivation for cocaine in rats. Here, we show that in outbred rats, the STN can modulate the motivation for alcohol according to alcohol preference, without affecting alcohol intake. When performed on 'HighDrinker' rats, STN lesions enhanced the breaking point (BP) under a progressive ratio schedule of reinforcement and increased the time spent in the environment previously paired with alcohol access in the place preference paradigm. In contrast, when performed on 'Low-Drinker' rats, STN lesions decreased the BP and increased the time spent in the environment paired with water. These results show that STN lesions enhance the motivation for alcohol in rats showing a high alcohol preference, whereas they decrease it in rats showing a low preference for alcohol. These results suggest that the STN plays a complex role in the reward circuit, that is not limited to a dissociation between motivation for natural rewards and drugs of abuse, but takes other factors, such as alcohol preference, into account.

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“…According to the current model of the basal ganglia functional organization (Albin et al, 1989), the degeneration of nigrostriatal DA neurons produces an upregulation of the striatopallidal GABA pathway (indirect pathway). The increased pallidal GABAergic activity induce the disinhibition of the STN and the SNr, which are overactive in Parkinsonian conditions and thought to be responsible of the reduced thalamocortical activity (DeLong, 1990).…”

Section: Functional Interaction Between a 2a And Mglu 5 Receptorsmentioning

confidence: 99%

“…In addition to the A 2A -D 2 receptors interaction, altered balance between DA-and glutamate neuronal systems may also underlie the pathophysiology of PD (Albin et al, 1989;Wichmann and DeLong, 1997). A growing number of studies in animal models of PD suggest that counteracting glutamatergic hyperactivity by pharmacological blockade of glutamate transmission in the basal ganglia represents the most recent challenge in the treatment of Parkinsonian patients (Rouse et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

Coccurello

Breysse

Amalric

2004

Neuropsychopharmacol

117

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Recent evidence suggest that antagonism of adenosine A 2A receptors represent an alternative therapeutic approach to Parkinson's disease (PD). Coactivation of A 2A and the glutamate subtype 5 metabotropic receptors (mGlu 5 ) synergistically stimulates DARPP-32 phosphorylation and c-fos expression in the striatum. This study therefore tested the effects of a joint blockade of these receptors to alleviate the motor dysfunction in a rat model of PD. 6-Hydroxydopamine infusions in the striatum produced akinetic deficits in rats trained to release a lever after a stimulus in a reaction time (RT) task. At 2 weeks after the lesion, A 2A and mGlu 5 receptors selective antagonists 8-(3-chlorostyryl)caffeine (CSC) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) were administered daily for 3 weeks either as a single or joint treatment. Injections of CSC (1.25 mg/kg) and MPEP (1.5 mg/kg) separately or in combination reduced the increase of delayed responses and RTs induced by 6-OHDA lesions, while the same treatment had no effect in controls. Furthermore, coadministration of lower doses of 0.625 mg/kg CSC and 0.375 mg/kg MPEP noneffective as a single treatment promoted a full and immediate recovery of akinesia, which was found to be more efficient than the separate blockade of these receptors. These results demonstrate that the combined inactivation of A 2A and mGlu 5 receptor potentiate their beneficial effects supporting this pharmacological strategy as a promising anti-Parkinsonian therapy.

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The functional anatomy of disorders of the basal ganglia

Cited by 529 publications

References 10 publications

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

Alcohol Preference Influences the Subthalamic Nucleus Control on Motivation for Alcohol in Rats

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

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