CiteULike: Tag basalganglia

Functional architecture of basal ganglia circuits: neural substrates of parallel processing.

GE Alexander — 2006-12-27T12:18:41-00:00

Trends Neurosci, Vol. 13, No. 7. (July 1990), pp. 266-271.

Concepts of basal ganglia organization have changed markedly over the past decade, due to significant advances in our understanding of the anatomy, physiology and pharmacology of these structures. Independent evidence from each of these fields has reinforced a growing perception that the functional architecture of the basal ganglia is essentially parallel in nature, regardless of the perspective from which these structures are viewed. This represents a significant departure from earlier concepts of basal ganglia organization, which generally emphasized the serial aspects of their connectivity. Current evidence suggests that the basal ganglia are organized into several structurally and functionally distinct 'circuits' that link cortex, basal ganglia and thalamus, with each circuit focused on a different portion of the frontal lobe. In this review, Garrett Alexander and Michael Crutcher, using the basal ganglia 'motor' circuit as the principal example, discuss recent evidence indicating that a parallel functional architecture may also be characteristic of the organization within each individual circuit.

Contributions of an avian basal ganglia-forebrain circuit to real-time modulation of song

Mimi Kao — 2005-02-15T01:35:48-00:00

Nature, Vol. 433, No. 7026. (10 February 2005), pp. 638-643.

Evidence for Differential Cortical Input to Direct Pathway versus Indirect Pathway Striatal Projection Neurons in Rats

Wanlong Lei — 2006-09-28T07:58:32-00:00

J. Neurosci., Vol. 24, No. 38. (22 September 2004), pp. 8289-8299.

The two main types of corticostriatal neurons are those that project only intratelencephalically (IT-type), the intrastriatal terminals of which are 0.41 microm in mean diameter, and those that send their main axon into pyramidal tract and have a collateral projection to striatum (PT-type), the intrastriatal terminals of which are 0.82 microm in mean diameter. We used three approaches to examine whether the two striatal projection neuron types (striatonigral direct pathway vs striatopallidal indirect pathway) differ in their input from IT-type and PT-type neurons. First, we retrogradely labeled one striatal projection neuron type or the other with biotinylated dextran amine (BDA)-3000 molecular weight. We found that terminals making asymmetric axospinous contact with striatonigral neurons were 0.43 microm in mean diameter, whereas those making asymmetric axospinous contact with striatopallidal neurons were 0.69 microm. Second, we preferentially immunolabeled striatonigral neurons for D1 dopamine receptors or striatopallidal neurons for D2 dopamine receptors and found that axospinous terminals had a smaller mean size (0.45 microm) on D1+ spines than on D2+ spines (0.61 microm). Finally, we combined selective BDA labeling of IT-type or PT-type terminals with immunolabeling for D1 or D2, and found that IT-type terminals were twice as common as PT-type on D1+ spines, whereas PT-type terminals were four times as common as IT-type on D2+ spines. These various results suggest that striatonigral neurons preferentially receive input from IT-type cortical neurons, whereas striatopallidal neurons receive greater input from PT-type cortical neurons. This differential cortical connectivity may further the roles of the direct and indirect pathways in promoting desired movements and suppressing unwanted movements, respectively. 10.1523/JNEUROSCI.1990-04.2004

The functional anatomy of disorders of the basal ganglia.

RL Albin — 2006-12-27T12:17:09-00:00

Trends Neurosci, Vol. 18, No. 2. (February 1995), pp. 63-64.

Stimulus-specific plasticity of prefrontal cortex dopamine neurotransmission.

ME Jackson — 2007-02-18T14:19:22-00:00

J Neurochem, Vol. 88, No. 6. (March 2004), pp. 1327-1334.

Future planning and behavioral modification is thought to require experience-dependent plasticity in neuronal circuits involving the prefrontal cortex, nucleus accumbens and amygdala. Dopamine has been implicated in such plasticity; however, the nature of the adaptive response of dopamine systems to emotionally salient experiences is poorly understood. We determined whether the dopaminergic response to a given stimulus changes after the first exposure to that stimulus and whether this alteration is stimulus specific. Dopamine release was measured in the prefrontal cortex and the nucleus accumbens in response to two aversive but qualitatively distinct stimuli, physical restraint and electrical microstimulation of basolateral amygdala. In the prefrontal cortex, the first exposure to restraint or amygdala stimulation produced similar increases in dopamine release. The second exposure to restraint resulted in an attenuated response (- 36%) whereas the second exposure to amygdala stimulation produced a potentiated response (+ 110%). Cross-modal potentiation of response occurred with both stimuli. These adaptive changes were specific to the prefrontal cortex and were not observed in the nucleus accumbens. These findings demonstrate that prefrontal cortical dopamine output adapts after a single exposure to stimuli with emotional salience. The direction of this adaptation, however, is not uniform and depends on the nature of the stimulus.

A Computational Model of How the Basal Ganglia Produce Sequences

Gregory Berns — 2005-12-12T16:17:14-00:00

Journal of Cognitive Neuroscience, Vol. 10, No. 1. (1 January 1998), pp. 108-121.

We propose a systems-level computational model of the basal ganglia based closely on known anatomy and physiology. First, we assume that the thalamic targets, which relay ascending information to cortical action and planning areas, are tonically inhibited by the basal ganglia. Second, we assume that the output stage of the basal ganglia, the internal segment of the globus pallidus (GPi), selects a single action from several competing actions via lateral interactions. Third, we propose that a form of local working memory exists in the form of reciprocal connections between the external globus pallidus (GPe) and the subthalamic nucleus (STN). As a test of the model, the system was trained to learn a sequence of states that required the context of previous actions. The striatum, which was assumed to represent a conjunction of cortical states, directly selected the action in the GP during training. The STN-to-GP connection strengths were modified by an associative learning rule and came to encode the sequence after 20 to 40 iterations through the sequence. Subsequently, the system automatically reproduced the sequence when cued to the first action. The behavior of the model was found to be sensitive to the ratio of the striatal-nigral learning rate to the STN-GP learning rate. Additionally, the degree of striatal inhibition of the globus pallidus had a significant influence on both learning and the ability to select an action. Low learning rates, which would be hypothesized to reflect low levels of dopamine, as in Parkinson's disease, led to slow acquisition of contextual information. However, this could be partially offset by modeling a lesion of the globus pallidus that resulted in an increase in the gain of the STN units. The parameter sensitivity of the model is discussed within the framework of existing behavioral and lesion data.

Computational Explorations in Cognitive Neuroscience: Understanding the Mind by Simulating the Brain

Randall O'Reilly — 2006-05-11T14:07:36-00:00

(04 September 2000)

The goal of computational cognitive neuroscience is to understand how the brain embodies the mind by using biologically based computational models comprising networks of neuronlike units. This text, based on a course taught by Randall O'Reilly and Yuko Munakata over the past several years, provides an in-depth introduction to the main ideas in the field. The neural units in the simulations use equations based directly on the ion channels that govern the behavior of real neurons, and the neural networks incorporate anatomical and physiological properties of the neocortex. Thus the text provides the student with knowledge of the basic biology of the brain as well as the computational skills needed to simulate large-scale cognitive phenomena.<br /> <br /> The text consists of two parts. The first part covers basic neural computation mechanisms: individual neurons, neural networks, and learning mechanisms. The second part covers large-scale brain area organization and cognitive phenomena: perception and attention, memory, language, and higher-level cognition. The second part is relatively self-contained and can be used separately for mechanistically oriented cognitive neuroscience courses. Integrated throughout the text are more than forty different simulation models, many of them full-scale research-grade models, with friendly interfaces and accompanying exercises. The simulation software (PDP++, available for all major platforms) and simulations can be downloaded free of charge from the Web. Exercise solutions are available, and the text includes full information on the software.

Behavioural sensitization in addiction, schizophrenia, Parkinson's disease and dyskinesia.

WJ Schmidt — 2006-12-15T16:42:50-00:00

Neurotox Res, Vol. 10, No. 2. (October 2006), pp. 161-166.

Incentive learning takes place when dopaminergic neurons are activated, usually by rewards. As a result, previously neutral stimuli associated with reward acquire incentive salience and thus the ability to elicit approach or other responses in the future. Incentive learning is assumed to underlie psychostimulant-induced context-dependent sensitization that may play a prominent role in the development of addiction, in dyskinesia, and in amphetamine-induced psychosis. Assuming that these pathological states are due to the gradual process of sensitization, the effects of therapeutics might be manifested as a gradual desensitization. This assumption could explain the delay between onset of cellular effects of drugs (e.g., dopamine receptor blockade) and the improvement in symptoms (e.g., decreases in psychotic symptoms). Reduced dopamine activity results in behavioural changes that are opposite to psychostimulant-induced sensitization, i.e., rewarded behaviours decline in an extinction-like fashion despite the presence and consumption of rewards. We show here that also non reward-related behaviour, i.e., motor activity and catalepsy, follows the same rules: motility is not switched off by dopamine receptor blockade or by 6-hydroxydopamine lesions, but shows a test-to-test extinction-like decline. Thus, psychostimulant-induced sensitization and dopamine-deficiency induced decline of behaviour follows similar rules but in opposite directions.

The short-latency dopamine signal: a role in discovering novel actions?

Peter Redgrave — 2006-11-20T22:53:28-00:00

Nature Reviews Neuroscience, Vol. 7, No. 12. (08 November 2006), pp. 967-975.

The persistence of behavioral sensitization to cocaine parallels enhanced inhibition of nucleus accumbens neurons

Dj Henry — 2006-10-27T13:33:25-00:00

J. Neurosci., Vol. 15, No. 9. (1 September 1995), pp. 6287-6299.

The thalamostriatal system: a highly specific network of the basal ganglia circuitry.

Y Smith — 2005-06-15T14:17:39-00:00

Trends Neurosci, Vol. 27, No. 9. (September 2004), pp. 520-527.

Although the existence of thalamostriatal projections has long been known, the role(s) of this system in the basal ganglia circuitry remains poorly characterized. The intralaminar and ventral motor nuclei are the main sources of thalamic inputs to the striatum. This review emphasizes the high degree of anatomical and functional specificity of basal ganglia-thalamostriatal projections and discusses various aspects of the synaptic connectivity and neurochemical features that differentiate this glutamate system from the corticostriatal network. It also discusses the importance of thalamostriatal projections from the caudal intralaminar nuclei in the process of attentional orientation. A major task of future studies is to characterize the role(s) of corticostriatal and thalamostriatal pathways in regulating basal ganglia activity in normal and pathological conditions.

The basal ganglia: a vertebrate solution to the selection problem?

P Redgrave — 2006-12-06T12:41:58-00:00

Neuroscience, Vol. 89, No. 4. (1999), pp. 1009-1023.

A selection problem arises whenever two or more competing systems seek simultaneous access to a restricted resource. Consideration of several selection architectures suggests there are significant advantages for systems which incorporate a central switching mechanism. We propose that the vertebrate basal ganglia have evolved as a centralized selection device, specialized to resolve conflicts over access to limited motor and cognitive resources. Analysis of basal ganglia functional architecture and its position within a wider anatomical framework suggests it can satisfy many of the requirements expected of an efficient selection mechanism.

The basal ganglia: focused selection and inhibition of competing motor programs.

JW Mink — 2006-06-06T00:50:57-00:00

Prog Neurobiol, Vol. 50, No. 4. (November 1996), pp. 381-425.

The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these a abnormalities. However, it has not been agreed just what the basal ganglia contribute to normal movement. Recent advances in knowledge of the basal ganglia circuitry, activity of basal ganglia neurons during movement, and the effect of basal ganglia lesions have led to a new hypothesis of basal ganglia function. The hypothesis states that the basal ganglia do not generate movements. Instead, when voluntary movement is generated by cerebral cortical and cerebellar mechanisms, the basal ganglia act broadly to inhibit competing motor mechanisms that would otherwise interfere with the desired movement. Simultaneously, inhibition is removed focally from the desired motor mechanisms to allow that movement to proceed. Inability to inhibit competing motor programs results in slow movements, abnormal postures and involuntary muscle activity.

Opposing basal ganglia processes shape midbrain visuomotor activity bilaterally

Huai Jiang — 2006-12-06T12:39:03-00:00

Nature, Vol. 423, No. 6943. (26 June 2003), pp. 982-986.

A computational model of action selection in the basal ganglia. II. Analysis and simulation of behaviour.

K Gurney — 2006-06-06T04:10:48-00:00

Biol Cybern, Vol. 84, No. 6. (June 2001), pp. 411-423.

In a companion paper a new functional architecture was proposed for the basal ganglia based on the premise that these brain structures play a central role in behavioural action selection. The current paper quantitatively describes the properties of the model using analysis and simulation. The decomposition of the basal ganglia into selection and control pathways is supported in several ways. First, several elegant features are exposed--capacity scaling, enhanced selectivity and synergistic dopamine modulation--which might be expected to exist in a well designed action selection mechanism. The discovery of these features also lends support to the computational premise of selection that underpins our model. Second, good matches between model globus pallidus external segment output and globus pallidus internal segment and substantia nigra reticulata area output, and neurophysiological data, have been found which are indicative of common architectural features in the model and biological basal ganglia. Third, the behaviour of the model as a signal selection mechanism has parallels with some kinds of action selection observed in animals under various levels of dopaminergic modulation.

How laminar frontal cortex and basal ganglia circuits interact to control planned and reactive saccades

Joshua Brown — 2006-12-06T12:22:39-00:00

Neural Netw., Vol. 17, No. 4. (May 2004), pp. 471-510.

Neuronal Activity in Substantia Nigra Pars Reticulata during Target Selection

Michele Basso — 2006-12-06T12:19:35-00:00

J. Neurosci., Vol. 22, No. 5. (1 March 2002), pp. 1883-1894.

Complex visual scenes require that a target for an impending saccadic eye movement be selected from a number of possible targets. We investigated whether changing the number of stimuli from which a target would be identified altered the activity of substantia nigra pars reticulata (SNr) neurons of the basal ganglia (BG) and how such changes might contribute to changes we observed previously in the superior colliculus (SC). One, two, four, or eight visual stimuli appeared on random trials while monkeys fixated a centrally located spot. After a delay, one of the stimuli in the array changed luminance, indicating that it was the saccade target. We found that SNr neurons that had a pause in tonic activity after target onset and when the saccade was made to the target showed a modulation of activity during the multitarget task. Because the number of stimuli in the array increased from one to eight, the initial pause after the onset of the visual stimulus decreased. Activity during the preselection delay was reduced but was independent of the number of possible targets present. When one of the stimuli was identified as the saccade target, but before the saccade was made, we found a sharp decline in activity. This decline was related to the monkey's selecting the target rather than the luminance change identifying the target, because on error trials, when the luminance changed but a saccade was not made to the target, the activity did not decline. The decline for the preferred target location was also accompanied by a lesser decline for adjacent locations. Our findings indicate that SNr activity changes with target selection as it does with saccade initiation and that the SNr could make substantial, direct contributions to the SC at both times. The pause in SNr activity with target selection is consistent with the hypothesis that BG provide a disinhibition for the selection of desired movements.

Corticostriatal projections from layer V cells in rat are collaterals of long-range corticofugal axons.

M Levesque — 2006-10-13T12:25:44-00:00

Brain Res, Vol. 709, No. 2. (19 February 1996), pp. 311-315.

Corticostriatal projections arising from the infragranular layers of the motor and second somatosensory cortices were studied in rats after labeling small pools of neurons with biocytin. Camera lucida reconstruction of 263 fibers arising from laminae V and VI revealed that all corticostriatal projections derive from collaterals of lamina V cells whose main axons descend into the cerebral peduncle. In contrast, lamina VI cells do not branch upon the striatum, but upon the thalamus. Together with the results obtained in previous tracing studies, the present data raise the possibility that no neuron is exclusively corticostriatal. We therefore propose that all corticostriatal projections are collaterals given off by the axons of two types of neurons: layer V cells whose main axon project to the brainstem and/or spinal cord, and layer III cells that project to the contralateral hemisphere.

Biologically plausible error-driven learning using local activation differences: The generalized recirculation algorithm

R O'Reilly — 2006-08-09T05:42:44-00:00

(1996)

The error backpropagation learning algorithm (BP) is generally considered biologically implausible because it does not use locally available, activation-based variables. A version of BP that can be computed locally using bi-directional activation recirculation (Hinton & McClelland, 1988) instead of backpropagated error derivatives is more biologically plausible. This paper presents a generalized version of the recirculation algorithm (GeneRec), which overcomes several limitations of the...

Axonal arborizations of corticostriatal and corticothalamic fibers arising from the second somatosensory area in the rat.

M Lévesque — 2006-10-13T12:25:07-00:00

Cereb Cortex, Vol. 6, No. 6. (c 1996), pp. 759-770.

Corticostriatal and corticothalamic projections arising from the second somatosensory area in the rat were studied after labeling small pools of neurons in laminae V and VI with biocytin. Tracing the axon of single neurons revealed the following principles of organization: (i) all corticostriatal and corticothalamic projections arising from layer V cells are collaterals of long-range corticofugal axons that also project below the thalamic level; (ii) all layer V cells that project to the thalamus also project to the striatum; (iii) all layer VI corticothalamic cells project exclusively to the thalamus; (iv) cells of the upper part of lamina VI send collaterals to the thalamic reticular nucleus and arborize in the ventrobasal complex forming rod-like terminal fields; and (v) cells of the lower part of lamina VI also send collaterals to the thalamic reticular nucleus, give off few branches in the ventrobasal complex and terminate principally in the caudal part of the posterior thalamic group. On the basis of these findings, and in the light of previous anatomical studies, it is proposed that the above mentioned organizing principles represent general rules that also apply to corticostriatal and corticothalamic pathways arising from other areas of the neocortex.

Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism

Michael Frank — 2006-01-05T13:43:21-00:00

J. Cogn. Neurosci., Vol. 17, No. 1. (1 January 2005), pp. 51-72.

Dopamine (DA) depletion in the basal ganglia (BG) of Parkinson's patients gives rise to both frontal-like and implicit learning impairments. Dopaminergic medication alleviates some cognitive deficits but impairs those that depend on intact areas of the BG, apparently due to DA "overdose." These findings are difficult to accommodate with verbal theories of BG/DA function, owing to complexity of system dynamics: DA dynamically modulates function in the BG, which is itself a modulatory system. This article presents a neural network model that instantiates key biological properties and provides insight into the underlying role of DA in the BG during learning and execution of cognitive tasks. Specifically, the BG modulates the execution of "actions" (e.g., motor responses and working memory updating) being considered in different parts of the frontal cortex. Phasic changes in DA, which occur during error feedback, dynamically modulate the BG threshold for facilitating/suppressing a cortical command in response to particular stimuli. Reduced dynamic range of DA explains Parkinson and DA overdose deficits with a single underlying dysfunction, despite overall differences in raw DA levels. Simulated Parkinsonism and medication effects provide a theoretical basis for behavioral data in probabilistic classification and reversal tasks. The model also provides novel testable predictions for neuropsychological and pharmacological studies, and motivates further investigation of BG/DA interactions with the prefrontal cortex in working memory.

The basal ganglia.

AM Graybiel — 2007-01-11T16:59:59-00:00

Curr Biol, Vol. 10, No. 14. (13 July 2000)

Midbrain dopamine neurons encode decisions for future action

Genela Morris — 2006-07-26T12:30:16-00:00

Nature Neuroscience, Vol. 9, No. 8. (23 July 2006), pp. 1057-1063.

The ability of environmental context to facilitate psychomotor sensitization to amphetamine can be dissociated from its effect on acute drug responsiveness and on conditioned responding.

HS Crombag — 2007-04-05T15:04:11-00:00

Neuropsychopharmacology, Vol. 24, No. 6. (June 2001), pp. 680-690.

Doses of amphetamine or cocaine that fail to induce psychomotor sensitization when given to a rat in its home cage can produce robust sensitization if given immediately following placement into a relatively novel, distinct environment. A drug-associated context can serve as a conditioned stimulus, and therefore may promote robust sensitization by facilitating associative learning processes. We examined this hypothesis by habituating rats to the test environment for 1 or 6--8 hr prior to each drug injection, which degrades the ability of environmental context to serve as an effective conditioned stimulus. When 0.5 mg/kg of amphetamine was administered intravenously immediately after placement into a distinct environment there was a large acute psychomotor response (rotational behavior) on the first test day, and robust sensitization developed with repeated daily injections. When the same treatment was administered in the home cage, there was a small acute response and no sensitization developed. The enhanced acute response seen in the distinct environment was significantly attenuated by 1 hr of habituation to the test environment, and completely abolished by 6--8 hr of habituation. Also, as little as 1 hr of habituation completely prevented the development of a conditioned rotational response. In contrast, neither 1 nor 6--8 hr of habituation had any effect on the ability of amphetamine to induce robust behavioral sensitization. It is concluded that the ability of a distinct environment to facilitate sensitization to amphetamine can be dissociated from its effect on acute drug responsiveness and from the ability of drug-associated environmental stimuli to elicit a conditioned response. Possible mechanisms by which a distinct environment facilitates sensitization are discussed.

Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction

Nora Volkow — 2006-06-28T14:11:13-00:00

J. Neurosci., Vol. 26, No. 24. (14 June 2006), pp. 6583-6588.

The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studies have shown that with repeated drug exposure neutral stimuli paired with the drug (conditioned stimuli) start to increase dopamine by themselves, which is an effect that could underlie drug-seeking behavior. Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving. We tested eighteen cocaine-addicted subjects using positron emission tomography and [11C]raclopride (dopamine D2 receptor radioligand sensitive to competition with endogenous dopamine). We measured changes in dopamine by comparing the specific binding of [11C]raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [11C]raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction. 10.1523/JNEUROSCI.1544-06.2006

Context-dependent catalepsy intensification is due to classical conditioning and sensitization.

J Amtage — 2006-06-14T16:20:13-00:00

Behav Pharmacol, Vol. 14, No. 7. (November 2003), pp. 563-567.

Haloperidol-induced catalepsy represents a model of neuroleptic-induced Parkinsonism. Daily administration of haloperidol, followed by testing for catalepsy on a bar and grid, results in a day-to-day increase in catalepsy that is completely context dependent, resulting in a strong placebo effect and in a failure of expression after a change in context. The aim of this study was to analyse the associative learning process that underlies context dependency. Catalepsy intensification was induced by a daily threshold dose of 0.25 mg/kg haloperidol. Extinction training and retesting under haloperidol revealed that sensitization was composed of two components: a context-conditioning component, which can be extinguished, and a context-dependent sensitization component, which cannot be extinguished. Context dependency of catalepsy thus follows precisely the same rules as context dependency of psychostimulant-induced sensitization. Catalepsy sensitization is therefore due to conditioning and sensitization.

Catalepsy intensifies context-dependently irrespective of whether it is induced by intermittent or chronic dopamine deficiency.

A Klein — 2006-06-16T18:15:29-00:00

Behav Pharmacol, Vol. 14, No. 1. (February 2003), pp. 49-53.

It is well known that neuroleptic-induced catalepsy in rats intensifies upon repeated testing. Here, the question is addressed whether intensification of catalepsy results from intermittent drug administration or from intermittent context exposure. In experiment 1, rats were treated with intermittent haloperidol injections (0.25 mg/kg) followed by the catalepsy test (descent latency from the horizontal bar). In experiment 2, rats were lesioned with 6-hydroxydopamine injections into the striatum, resulting in a 45% reduction of dopamine concentration. Catalepsy was tested intermittently for several weeks. In both experiments we found a very stable intensification of catalepsy over 9 (haloperidol rats) and 11 (lesioned rats) days, showing that intensification is not due to intermittent dopamine depletion. In both experiments, intensification of catalepsy was very stable and was observed 18 days later in haloperidol-treated rats and 101 days later in lesioned animals. However, a change of the environmental context abolished the intensified catalepsy in both experiments. It is concluded that intensification of catalepsy is due to intermittent context exposure rather than intermittent drug administration. It is generally accepted that 6-hydroxydopamine lesions represent an animal model of Parkinson's disease. Given the results above, context-dependent intensification of parkinsonian symptoms might also occur in Parkinson's disease, and its prevention should be taken into consideration for future therapy of the disease.

Bidirectional activity-dependent plasticity at corticostriatal synapses.

E Fino — 2006-01-17T15:45:48-00:00

J Neurosci, Vol. 25, No. 49. (7 December 2005), pp. 11279-11287.

Corticostriatal projections originate from the entire cerebral cortex and provide the major source of glutamatergic inputs to the basal ganglia. Despite the importance of corticostriatal connections in sensorimotor learning and cognitive functions, plasticity forms at these synapses remain strongly debated. Using a corticostriatal slice preserving the connections between the somatosensory cortex and the target striatal cells, we report the induction of both non-Hebbian and Hebbian forms of long-term potentiation (LTP) and long-term depression (LTD) on striatal output neurons (SONs). LTP and LTD can be induced selectively by different stimulation patterns (high-frequency trains vs low-frequency pulses) and were evoked with similar efficiency in non-Hebbian and Hebbian modes. Combination of LTP-LTD and LTD-LTP sequences revealed that bidirectional plasticity occurs at the same SONs and provides efficient homeostatic mechanisms leading to a resetting of corticostriatal synapses avoiding synaptic saturation. The effect of temporal relationship between cortical stimulation and SON activity was assessed using spike-timing-dependent plasticity (STDP) protocols. An LTP was observed when an action potential was triggered in the striatal neuron before the cortical stimulus, and, conversely, an LTD was induced when the striatal neuron discharge was triggered after the cortical stimulation. Such STDP was reversed when compared with those described so far in other mammalian brain structures. This mechanism may be essential for the role of the striatum in learning of motor sequences in which sensory and motor events are associated in a precise time sequence.

Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications.

SJ Kish — 2006-12-06T10:11:18-00:00

N Engl J Med, Vol. 318, No. 14. (7 April 1988), pp. 876-880.

Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease.

Morphological and electrophysiological characteristics of pyramidal tract neurons in the rat

P Landry — 2006-10-13T10:24:22-00:00

Experimental Brain Research, Vol. V57, No. 1. (1 January 1984), pp. 177-190.

Making Working Memory Work: A Computational Model of Learning in the Prefrontal Cortex and Basal Ganglia

Randall O'Reilly — 2006-01-29T18:15:37-00:00

Neural Comp., Vol. 18, No. 2. (1 February 2005), pp. 283-328.

The prefrontal cortex has long been thought to subserve both working memory (the holding of information online for processing) and executive functions (deciding how to manipulate working memory and perform processing). Although many computational models of working memory have been developed, the mechanistic basis of executive function remains elusive, often amounting to a homunculus. This article presents an attempt to deconstruct this homunculus through powerful learning mechanisms that allow a computational model of the prefrontal cortex to control both itself and other brain areas in a strategic, task-appropriate manner. These learning mechanisms are based on subcortical structures in the midbrain, basal ganglia, and amygdala, which together form an actor-critic architecture. The critic system learns which prefrontal representations are task relevant and trains the actor, which in turn provides a dynamic gating mechanism for controlling working memory updating. Computationally, the learning mechanism is designed to simultaneously solve the temporal and structural credit assignment problems. The model's performance compares favorably with standard backpropagation-based temporal learning mechanisms on the challenging 1-2-AX working memory task and other benchmark working memory tasks.

Hold your horses: A dynamic computational role for the subthalamic nucleus in decision making.

Michael Frank — 2006-09-28T18:04:56-00:00

Neural Networks (29 August 2006)

The basal ganglia (BG) coordinate decision making processes by facilitating adaptive frontal motor commands while suppressing others. In previous work, neural network simulations accounted for response selection deficits associated with BG dopamine depletion in Parkinson's disease. Novel predictions from this model have been subsequently confirmed in Parkinson patients and in healthy participants under pharmacological challenge. Nevertheless, one clear limitation of that model is in its omission of the subthalamic nucleus (STN), a key BG structure that participates in both motor and cognitive processes. The present model incorporates the STN and shows that by modulating when a response is executed, the STN reduces premature responding and therefore has substantial effects on which response is ultimately selected, particularly when there are multiple competing responses. Increased cortical response conflict leads to dynamic adjustments in response thresholds via cortico-subthalamic-pallidal pathways. The model accurately captures the dynamics of activity in various BG areas during response selection. Simulated dopamine depletion results in emergent oscillatory activity in BG structures, which has been linked with Parkinson's tremor. Finally, the model accounts for the beneficial effects of STN lesions on these oscillations, but suggests that this benefit may come at the expense of impaired decision making.

Dopamine Modulation of State-Dependent Endocannabinoid Release and Long-Term Depression in the Striatum

Anatol Kreitzer — 2007-07-09T19:37:58-00:00

J. Neurosci., Vol. 25, No. 45. (9 November 2005), pp. 10537-10545.

Endocannabinoids are important mediators of short- and long-term synaptic plasticity, but the mechanisms of endocannabinoid release have not been studied extensively outside the hippocampus and cerebellum. Here, we examined the mechanisms of endocannabinoid-mediated long-term depression (eCB-LTD) in the dorsal striatum, a brain region critical for motor control and reinforcement learning. Unlike other cell types, strong depolarization of medium spiny neurons was not sufficient to yield detectable endocannabinoid release. However, when paired with postsynaptic depolarization sufficient to activate L-type calcium channels, activation of postsynaptic metabotropic glutamate receptors (mGluRs), either by high-frequency tetanic stimulation or an agonist, induced eCB-LTD. Pairing bursts of afferent stimulation with brief subthreshold membrane depolarizations that mimicked down-state to up-state transitions also induced eCB-LTD, which not only required activation of mGluRs and L-type calcium channels but also was bidirectionally modulated by dopamine D2 receptors. Consistent with network models, these results demonstrate that dopamine regulates the induction of a Hebbian form of long-term synaptic plasticity in the striatum. However, this gating of plasticity by dopamine is accomplished via an unexpected mechanism involving the regulation of mGluR-dependent endocannabinoid release. 10.1523/JNEUROSCI.2959-05.2005

By carrot or by stick: cognitive reinforcement learning in parkinsonism.

MJ Frank — 2006-12-13T10:26:30-00:00

Science, Vol. 306, No. 5703. (10 December 2004), pp. 1940-1943.

To what extent do we learn from the positive versus negative outcomes of our decisions? The neuromodulator dopamine plays a key role in these reinforcement learning processes. Patients with Parkinson's disease, who have depleted dopamine in the basal ganglia, are impaired in tasks that require learning from trial and error. Here, we show, using two cognitive procedural learning tasks, that Parkinson's patients off medication are better at learning to avoid choices that lead to negative outcomes than they are at learning from positive outcomes. Dopamine medication reverses this bias, making patients more sensitive to positive than negative outcomes. This pattern was predicted by our biologically based computational model of basal ganglia-dopamine interactions in cognition, which has separate pathways for "Go" and "NoGo" responses that are differentially modulated by positive and negative reinforcement.

Intensification of cataleptic response in 6-hydroxydopamine-induced neurodegeneration of substantia nigra is not dependent on the degree of dopamine depletion.

J Srinivasan — 2006-10-02T10:00:59-00:00

Synapse, Vol. 51, No. 3. (1 March 2004), pp. 213-218.

An intensification of catalepsy has been observed upon repeated testing in rats with permanent neurodegeneration of substantia nigra. Here, the question is addressed whether the rate of development of intensification of catalepsy upon repeated testing in the same context is dependent on dopamine level in the basal ganglia. Rats were lesioned with 2 microg or 6 microg of 6-hydroxydopamine in the median forebrain bundle to produce dopamine depletion in substantia nigra in two different proportions. Both groups were exposed to catalepsy tests for 7 successive days in the same context, and the context was changed on day 8. On day 9 the catalepsy test was repeated with the old context. After the completion of the behavioral experiments, various regions of basal ganglia were analyzed for dopamine and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methyl tyronine, and homovanillic acid. Lesions with 6 microg of 6-hydroxydopamine produced strong dopamine depletion (78%) and akinetic response in the catalepsy test on day 1. Repeated exposure of this group to the catalepsy tests in the same context produced intensification of cataleptic response. Changing the context on day 8 reduced catalepsy. Performing the experiments again with the old context on day 9 produced an intensified response. Lesions with 2 microg of 6-hydroxydopamine produced partial dopamine depletion (46%) without any motor disturbances. However, repeated exposure and context changes produced a similar pattern of catalepsy as in the 6 microg lesioned animals. These results indicate that the rate of building up of intensification of catalepsy is not dependent on the degree of dopamine depletion. It signifies the importance of context in the expression and augmentation of parkinsonian symptoms during the course of the disease to subjects with subthreshold dopaminergic neurodegeneration that could not produce motor disturbances alone. Prevention of context-dependent intensification of catalepsy could be beneficial in the treatment of Parkinson's disease.

Behavioural pharmacology of glutamate receptors in the basal ganglia.

WJ Schmidt — 2006-10-02T09:57:23-00:00

Neurosci Biobehav Rev, Vol. 21, No. 4. (July 1997), pp. 381-392.

Glutamate receptors play a major role in the transmitter balance within the basal ganglia (BG). N-methyl-D-aspartate (NMDA) receptor stimulation within the striatum acts behaviourally depressant while intrastriatal as well as systemic administration of NMDA receptor-antagonists have rather stimulatory effects despite the different profiles of non-competitive-, competitive NMDA receptor- and glycine site-antagonists. In animal models of Parkinson's disease all these NMDA receptor antagonists counteract parkinsonian symptoms or act synergistically with L-3,4-dihydroxyphenylalanine (L-DOPA). The strong locomotion-inducing effect of the non-competitive NMDA receptor antagonists is partly, but not fully, mediated by a dopamine (DA) release in the nucleus accumbens. Manipulations at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors produce poor behavioural effects. These, however, are different or even opposed to NMDA receptor mediated effects. Local infusions of AMPA receptor-antagonists into the BG output nuclei have an anti-parkinsonian effect but systemic injections are ineffective. These drugs even counteract the anti-parkinsonian effect of DA agonists and of non-competitive NMDA receptor antagonists as well as the DA releasing effects of the latter drugs. Only few data on the role of metabotropic receptors exist but the different receptor subtypes with different regional distribution represent a promising target for pharmacological interventions.

A computational substrate for incentive salience.

SM McClure — 2005-03-09T16:57:03-00:00

Trends Neurosci, Vol. 26, No. 8. (August 2003), pp. 423-428.

Theories of dopamine function are at a crossroads. Computational models derived from single-unit recordings capture changes in dopaminergic neuron firing rate as a prediction error signal. These models employ the prediction error signal in two roles: learning to predict future rewarding events and biasing action choice. Conversely, pharmacological inhibition or lesion of dopaminergic neuron function diminishes the ability of an animal to motivate behaviors directed at acquiring rewards. These lesion experiments have raised the possibility that dopamine release encodes a measure of the incentive value of a contemplated behavioral act. The most complete psychological idea that captures this notion frames the dopamine signal as carrying 'incentive salience'. On the surface, these two competing accounts of dopamine function seem incommensurate. To the contrary, we demonstrate that both of these functions can be captured in a single computational model of the involvement of dopamine in reward prediction for the purpose of reward seeking.

NMDA receptor antagonists do not block the development of sensitization of catalepsy, but make its expression state-dependent.

A Lanis — 2006-10-02T09:52:09-00:00

Behav Pharmacol, Vol. 12, No. 2. (April 2001), pp. 143-149.

Dopamine (DA) receptor blockade induces catalepsy in rats which increases in strength upon retesting. This increase in catalepsy represents a form of sensitization which has been shown to be completely context dependent. Sensitization of catalepsy therefore represents a good model for studying the neurobiological mechanisms underlying the interaction between the cellular effect of a drug (DA-receptor blockade) and the context. This study investigated whether glutamatergic mechanisms are involved in the development of sensitization. Rats were treated with either haloperidol or haloperidol plus an N-methyl-D-aspartate (NMDA) receptor antagonist. Haloperidol consistently induced catalepsy which developed sensitization upon retesting. Co-administration of D-CPPene (5 mg/kg and 10 mg/kg, i.p.), eliprodil (30 mg/kg, i.p.) or Ro 25-6981 (15 mg/kg, i.p.) did not have any effect on sensitization, although all three drugs exerted some anticataleptic effects. When sensitization developed under haloperidol plus NMDA receptor antagonist, the sensitized response was expressed only in the presence of the NMDA receptor antagonist. This strongly suggests that the NMDA receptor antagonists represent contextual stimuli to which catalepsy has been conditioned, and this implies that the expression of sensitization has been rendered state-dependent.

Intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine.

WJ Schmidt — 2006-10-02T09:47:18-00:00

Psychopharmacology (Berl), Vol. 90, No. 1. (1986), pp. 123-130.

DL-2-amino-5-phosphonovaleric acid (AP-5), which blocks glutamatergic transmission at the NMDA-preferring receptor, was injected into the antero-dorsal striatum of rats. AP-5-induced behavioural changes were assessed i) using a stereotypy rating scale and ii) using an experimental chamber designed to quantify sniffing. In both behavioural situations it was shown that AP-5 (10 micrograms/0.5 microliter) induced continuous intensive sniffing similar to that induced by small doses of systemically administered amphetamine or apomorphine. However, oral stereotypies were not induced by AP-5. Systemically injected clozapine (5 and 10 mg/kg SC) as well as haloperidol (0.1 mg/kg IP) antagonized AP-5-induced sniffing. These results show that besides dopamine receptors, NMDA receptors are involved in the control of sniffing. In behavioural terms, the effect of glutamate mediated by the NMDA receptor in the striatum is opposite to that of dopamine.

Involvement of human basal ganglia in offline feedback control of voluntary movement.

P Brown — 2007-01-02T10:20:32-00:00

Curr Biol, Vol. 16, No. 21. (7 November 2006), pp. 2129-2134.

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.

Microcircuitry of the direct and indirect pathways of the basal ganglia

Y Smith — 2006-06-06T01:21:51-00:00

Neuroscience, Vol. 86, No. 2. (September 1998), pp. 353-387.

Our understanding of the organization of the basal ganglia has advanced markedly over the last 10 years, mainly due to increased knowledge of their anatomical, neurochemical and physiological organization. These developments have led to a unifying model of the functional organization of the basal ganglia in both health and disease. The hypothesis is based on the so-called "direct" and "indirect" pathways of the flow of cortical information through the basal ganglia and has profoundly influenced the field of basal ganglia research, providing a framework for anatomical, physiological and clinical studies. The recent introduction of powerful techniques for the analysis of neuronal networks has led to further developments in our understanding of the basal ganglia. The objective of this commentary is to build upon the established model of the basal ganglia connectivity and review new anatomical findings that lead to the refinement of some aspects of the model. Four issues will be discussed. (1) The existence of several routes for the flow of cortical information along "indirect" pathways. (2) The synaptic convergence of information flowing through the "direct" and "indirect" pathways at the single-cell level in the basal ganglia output structures. (3) The convergence of functionally diverse information from the globus pallidus and the ventral pallidum at different levels of the basal ganglia. (4) The interconnections between the two divisions of the pallidal complex and the subthalamic nucleus and the characterization of the neuronal network underlying the indirect pathways. The findings summarized in this commentary confirm and elaborate the models of the direct and indirect pathways of information flow through the basal ganglia and provide a morphological framework for future studies.

A robot model of the basal ganglia: behavior and intrinsic processing.

Tony Prescott — 2006-06-06T01:06:14-00:00

Neural Networks, Vol. 19, No. 1. (January 2006), pp. 31-61.

The existence of multiple parallel loops connecting sensorimotor systems to the basal ganglia has given rise to proposals that these nuclei serve as a selection mechanism resolving competitions between the alternative actions available in a given context. A strong test of this hypothesis is to require a computational model of the basal ganglia to generate integrated selection sequences in an autonomous agent, we therefore describe a robot architecture into which such a model is embedded, and require it to control action selection in a robotic task inspired by animal observations. Our results demonstrate effective action selection by the embedded model under a wide range of sensory and motivational conditions. When confronted with multiple, high salience alternatives, the robot also exhibits forms of behavioral disintegration that show similarities to animal behavior in conflict situations. The model is shown to cast light on recent neurobiological findings concerning behavioral switching and sequencing.

Model of Cortical-Basal Ganglionic Processing: Encoding the Serial Order of Sensory Events

David Beiser — 2006-06-06T00:26:56-00:00

Journal of Neurophysiology, Vol. 79, No. 6. (1 June 1998), pp. 3168-3188.

Several lines of evidence suggest that the prefrontal (PF) cortex and basal ganglia are important in cognitive aspects of serial order in behavior. We present a modular neural network model of these areas that encodes the serial order of events into spatial patterns of PF activity. The model is based on the topographically specific circuits linking the PF with the basal ganglia. Each module traces a pathway from the PF, through the basal ganglia and thalamus, and back to the PF. The complete model consists of an array of modules interacting through recurrent corticostriatal projections and collateral inhibition between striatal spiny units. The model's architecture positions spiny units for the classification of cortical contexts and events and provides bistable cortical-thalamic loops for sustaining a representation of these contextual events in working memory activations. The model was tested with a simulated version of a delayed-sequencing task. In single-unit studies, the task begins with the presentation of a sequence of target lights. After a short delay, the monkey must touch the targets in the order in which they were presented. When instantiated with randomly distributed corticostriatal weights, the model produces different patterns of PF activation in response to different target sequences. These patterns represent an unambiguous and spatially distributed encoding of the sequence. Parameter studies of these random networks were used to compare the computational consequences of collateral and feed-forward inhibition within the striatum. In addition, we studied the receptive fields of 20,640 model units and uncovered an interesting set of cue-, rank- and sequence-related responses that qualitatively resemble responses reported in single unit studies of the PF. The majority of units respond to more than one sequence of stimuli. A method for analyzing serial receptive fields is presented and utilized for comparing the model units to single-unit data.

Basal ganglia and cerebellar loops: motor and cognitive circuits

Frank Middleton — 2006-01-06T14:04:35-00:00

Brain Research Reviews, Vol. 31, No. 2. (March 2000), pp. 236-250.

The traditional view that the basal ganglia and cerebellum are simply involved in the control of movement has been challenged in recent years. One of the pivotal reasons for this reappraisal has been new information about basal ganglia and cerebellar connections with the cerebral cortex. In essence, recent anatomical studies have revealed that these connections are organized into discrete circuits or ‘ loops’. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia and cerebellum. The properties of neurons within the basal ganglia or cerebellar components of these circuits resembles the properties of neurons within the cortical areas subserved by these loops. For example, neuronal activity within basal ganglia and cerebellar loops with motor areas of the cerebral cortex is highly correlated with parameters of movement, while neuronal activity within basal ganglia and cerebellar loops with areas of the prefrontal cortex is more related to aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Studies of basal ganglia and cerebellar pathology support this conclusion. Damage to the basal ganglia or cerebellar components of circuits with motor areas of cortex leads to motor symptoms, whereas damage of the subcortical components of circuits with non-motor areas of cortex causes higher-order deficits. In this report, we review some of the new anatomical, physiological and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex.

Information processing, dimensionality reduction and reinforcement learning in the basal ganglia

Izhar Bar-Gad — 2006-01-16T16:16:44-00:00

Progress in Neurobiology, Vol. 71, No. 6. (December 2003), pp. 439-473.

Modeling of the basal ganglia has played a major role in our understanding of this elusive group of nuclei. Models of the basal ganglia have undergone evolutionary and revolutionary changes over the last 20 years, as new research in the fields of anatomy, physiology and biochemistry of these nuclei has yielded new information. Early models dealt with a single pathway through the nuclei and focused on the nature of the processing performed within it, convergence of information versus parallel processing of information. Later, the Albin-DeLong "box-and-arrow" model characterized the inter-nuclei interaction as multiple pathways while maintaining a simplistic scalar representation of the nuclei themselves. This model made a breakthrough by providing key insights into the behavior of these nuclei in hypo- and hyper-kinetic movement disorders. The next generation of models elaborated the intra-nuclei interactions and focused on the role of the basal ganglia in action selection and sequence generation which form the most current consensus regarding basal ganglia function in both normal and pathological conditions. However, new findings challenge these models and point to a different neural network approach to information processing in the basal ganglia. Here, we take an in-depth look at the reinforcement driven dimensionality reduction (RDDR) model which postulates that the basal ganglia compress cortical information according to a reinforcement signal using optimal extraction methods. The model provides new insights and experimental predictions on the computational capacity of the basal ganglia and their role in health and disease.

Computational models of the basal ganglia

Andrew Gillies — 2006-05-07T17:41:13-00:00

Movement Disorders, Vol. 15, No. 5. (September 2000), pp. 762-770.

Computer simulation studies and mathematical analysis of models of the basal ganglia are being used increasingly to explore theories of basal ganglia function. We review the implications of these new models for a general understanding of basal ganglia function in normal as well as in diseased brains. The focus is on their functional similarities rather than on the details of mathematical methodologies and simulation techniques. Most of the models suggest a vital role for the basal ganglia in learning. Although this interest in learning is partly driven by experimental results associating the acute firing of dopamine cells with reward prediction in monkeys, some of the models have preceded the electrophysiological results. Another common theme of the models is selection. In this case, the striatum is seen as detecting and selecting cortical contexts for access to basal ganglia output. Although the behavioral consequences of this selection are hard to define, the models provide frameworks within which to explore these ideas empirically. This provides a means of refining our understanding of basal ganglia function and to consider dysfunction within the new logical frameworks.

An Essay on the Shaking Palsy

James Parkinson — 2006-05-31T21:33:14-00:00

J Neuropsychiatry Clin Neurosci, Vol. 14, No. 2. (1 May 1817), pp. 223-236.

10.1176/appi.neuropsych.14.2.223

The basal ganglia and adaptive motor control.

AM Graybiel — 2006-01-06T11:56:58-00:00

Science, Vol. 265, No. 5180. (23 September 1994), pp. 1826-1831.

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Complementary roles of basal ganglia and cerebellum in learning and motor control.

K Doya — 2005-10-27T08:04:43-00:00

Curr Opin Neurobiol, Vol. 10, No. 6. (December 2000), pp. 732-739.

The classical notion that the basal ganglia and the cerebellum are dedicated to motor control has been challenged by the accumulation of evidence revealing their involvement in non-motor, cognitive functions. From a computational viewpoint, it has been suggested that the cerebellum, the basal ganglia, and the cerebral cortex are specialized for different types of learning: namely, supervised learning, reinforcement learning and unsupervised learning, respectively. This idea of learning-oriented specialization is helpful in understanding the complementary roles of the basal ganglia and the cerebellum in motor control and cognitive functions.

Representation of action-specific reward values in the striatum.

K Samejima — 2005-11-30T17:36:20-00:00

Science, Vol. 310, No. 5752. (25 November 2005), pp. 1337-1340.

The estimation of the reward an action will yield is critical in decision-making. To elucidate the role of the basal ganglia in this process, we recorded striatal neurons of monkeys who chose between left and right handle turns, based on the estimated reward probabilities of the actions. During a delay period before the choices, the activity of more than one-third of striatal projection neurons was selective to the values of one of the two actions. Fewer neurons were tuned to relative values or action choice. These results suggest representation of action values in the striatum, which can guide action selection in the basal ganglia circuit.